the relevance of early life environmental and …...1 Research Director Early Life Development,...
Transcript of the relevance of early life environmental and …...1 Research Director Early Life Development,...
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Research Director Early Life Development, Early Life Nutrition, Nutricia Research
Prof. Nutritional Programming, Dept Pediatrics, UMCG, Groningen
Brain health throughout life:
the relevance of early life
environmental and nutritional factorsEline M. van der Beek
EARLY LIFE: AN OPPORTUNITY FOR PREVENTION OF NON-COMMUNICABLE DISEASES
Gluckman PD J DOHaD 2010:1(01) pp 6-18. adapted with permission 2
Life course
Fixed genetic
contribution
is small
Role of
nutrition
Timely intervention
may produce
substantial risk
reduction
Impact of late
prevention or
treatment is small
primary
tertiary
secondary
Healthy aging
primordial
Chro
nic
Dis
ease R
isk
3
Dietary intakes change dramatically over
the first two years of life
Gidding S S et al. Circulation. 2005;112:2061-2075
MATERNAL
NUTRITION
PLACENTA
BREAST
MILK
GI TRACT
0-9
NUTRITIONAL REALITY IN INFANTS & TODDLERS:
Switz.
China
Indonesia
Egypt Saudi Arabia
Vietnam
Kenya
Cameroon
Morocco
Ivory
Coast
Portugal
Lebanon
Nigeria
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Burkina
Faso
Algeria
India
France
Brazil
MalaysiaSingapore
Thailand
Hong
Kong
Russia
Mexico
Canada
South Africa
Japan
UK
Austria
Germany
Bangladesh
USA Italy
NL
Spain
Tunesia
Senegal
Overseasterritories
Greece
HungaryBelgium
Ireland
Argentina
Myanmar
Uruguay
Iran
SwitzPoland
Turkey
Congo
Colombia
Azebaidjan
Cambodge
Chili
Bolivia
Scope nutritional reality in 3
steps:
1. Literature search and
expert interviews (40)
2. Dietary surveys (14)
3. Nutrient status studies (4)
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Babies & Mothers*, Children, Adults
Babies & Mothers*
Children, Adults
Seniors
TARGET POPULATIONS
BRAIN DEVELOPMENT CONTINUES THROUGHOUT CHILDHOOD
AND ADOLESCENCE
Morgane et al, Neurosci Biobehav Rev, 2002; Lauritzen et al, Prog Lipid Res, 2001 %
Siz
e o
fad
ult
0
20
40
60
80
100
120
140
160
0 1 2 4 6 8 10 14 18
Thymus
Brain
Testes
Body weight
Liver
Heart
Age (years)Brain growth:1- Waves of intense branching, building connections 2- Selective reduction of neurons and connections shapes functionality:
a- between 3 and 6 yearsb- during puberty (12-14 yrs)
3- The brain is only fully functionally mature in early adult hood (23 yrs)
neuron – dendrite
increaseconnections
selective
neuron loss
HUMAN BRAIN GROWTH & MATURATION:
Brain weight peaks at birth and represents 27% of adult brain weight
Brain maturation consists of sequences of specificevents like gliosis, myelinization and enruogenesis
60% of the adult brain weight is composed of lipids
Lipids, in particular essential fatty acids, are the main brain building blocks and essential for brain growth, brain maturation as well as maintenance……
Rapid brain growth as well as DHA accumulation takes place between conception and 2 yrs of age
Morgane et al, Neurosci Biobehav Rev, 2002; Lauritzen et al, Prog Lipid Res, 2001
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THE IMPORTANCE OF FAT IN HUMAN MILK
Lactose
53-61 g/L
Fat
30-50 g/L
Protein
9-10 g/L2’FL
1.1 g/LHMOS
10-12 g/L
MCT medium chain triglycerides, Lauric acid C12:0, Palmitic acid C16:0, Stearic acid C18:0, Oleic acid C18:1n9,
LA linoleic acid C18:2n6, ALA alpha-linolenic acid C18:3n3, DHA docosahexaenoic acid C22:6n3, ARA arachidonic acid C20:4n6
• Lipids provide 45-60% of the energy in
human milk
• The lipid contribution is stable over the
course of lactation
• The majority of lipids is composed of
fatty acids (FA)
• Milk FA composition is influenced by the
diet
CompositionQuantity
WHAT HAS CHANGED IN OUR DIET?
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omega 3
(n-3 PUFA)
Ailhaud et al, 2006; Gibson et al, 2010; McInnes et al, 2011, Muhlhausler et al, 2009, 2013
Lassek &Gaulin, 2014; Bernard et al, 2015
• Increased intake of n-6 PUFA + similar (or decreased) intake of n-3 PUFA
• Altered human milk FA composition & n6/n3 ratio
➢ Directly affects adipose tissue development
➢ Influences the development of the immune system
➢ LC-PUFAs are building blocks for all membranes
➢ DHA (ARA) support rapid brain growth & functional development
➢ Diets that differ in n6/n3 ratio affect neuronal development and adequate pruning
➢ High breast milk LA (N6) is negatively correlated to infant cognitive outcomes
Fat quality:
same quantity, different composition
omega 6
(n-6 PUFA)
=
REDUCING MATERNAL DIETARY LA SUPPLY IMPROVESOFFSPRING BRAIN N3PUFA ACCUMULATION
LOWn-6 diet
P2 start diet
P0
P5 P10 P16 P21offspring
Control diet
brain Fatty Acid
composition
End expP21
birth
% o
f to
tal bra
in F
A%
of
tota
l bra
in F
A
**
* ** **
*
*
*
LOWn-6 diet
Control diet
11,0
12,0
13,0
14,0
15,0
P5 P10 P16 P21
DHAC22:6n-3
0,0
0,1
0,2
0,3
0,4
0,5
P5 P10 P16 P21
n-3DPAC22:5n-3
0,00
0,05
0,10
P5 P10 P16 P21
EPAC20:5n-3
0,0
0,5
1,0
1,5
P5 P10 P16 P21
n-6DPAC22:5n-6
0,0
1,0
2,0
3,0
4,0
P5 P10 P16 P21
AdrAC22:4n-6
5,0
7,0
9,0
11,0
13,0
15,0
P5 P10 P16 P21
ARAC20:4n-6
*
* *
*
*
*#
**
Brain n-3
PUFA
Brain n-6
PUFA
lactating mother
ctrl
Low n6
Schipper et al. PLEFA, 2016
bloodstream
perinatal high fat diet
IR -> adiposity
[leptin surge] (neurotrophic)
malformation axons
(permanent)
impaired function
Overeating / obesityNutrients
(e.g. FA)
EARLY LIFE NUTRITON AFFECTSHYPOTHALAMIC SATIETY REGULATION
Structural formation of axons is steered by the nutritional environment
Simerly, Physiol & Behav, 2008
DEVELOPMENT OF HYPOTHALAMIC CIRCUITRY IS ALTERED BY DIETARY N6/N3 PUFA
Postnatal +n3 and low LA reduce density of ARH fibers
These effects were sustained into adulthood following a WSD challenge
Schipper et al, AJCN, 2013
EARLY LIFE DIET FATTY ACID COMPOSITION & LATER ADIPOSITY RISK
Oosting et al, Pediatr Res. 2010; Oosting et al, Nutr Res. 2016
ctrl
+DHA
ctrl
Low n6
EXP diet
EARLY LIFE STRESS INDUCES METABOLIC AND COGNITIVE DEFICITS
IN LATER LIFE
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A diet with reduced omega-6 to omega-3 fatty acid ratio in the early life:
1- prevented early-life stress induced cognitive impairments in behavioral testing in adulthood
(PN180)
2- prevented ELS induced reduction in cell survival in adulthood (PN245)
PhD thesis K. Yam 2018; collaboration with Dr. A. Korosi & Prof Dr. P. Lucassen, Univ Amsterdam
Yam et al, Psychoneuroendocrinology, 2017
INFANTS AT RISK OF LATER LIFE NCDs
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Obesogenic
environment LGA SGA
Maternal
GDM
Maternal
obesity Preterm
Large
at 1 yrUnbalanced
growth 0-12 moIncreased
adiposity
TOFI
Increased NCD risk: (childhood) obesity, cardio-metabolic disease, neurological disease
Stunting, wasting
& malnutrition
BIRTH
WEIGHT
POSTNATAL
GROWTH
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SGA
Preterm
1- Postnatal growth in preterm infants affects later health outcomes,
e.g. cardiometabolic risks and cognitive impairments
2- Postnatal growth in infants born term but small for gestational age
is associated with later adverse cognitive and metabolic outcomes
3- Dietary intervention during GDM can reduce birth weight as a
result of well controlled maternal hyperglycemia, but is still a risk
factor for higher infant growth and adiposity despite exclusive breast
feeding
Maternal
GDM
Ong et al, 2015, Acta Pediatrica, 104:974-86; Castanys-Muñoz E et al 2017, Acta Paediatrica, 106:1230-
38; Yamamoto et al, 2018, Diabetes Care, 41:1346-1361; Logan et al 2016, Diabetes Care, 39:1045-51,
ACADEMIC-INDUSTRY EXPERT CONSULTATIONILSI INSTITUTE FOR LIFE SCIENCES, EUROPE
• Reduced insulin
sensitivity
• Altered nutrient flux
to the fetus
(↑AA and FFA)
• Obesity risk
GDM DRIVES LATER DIABETES AND OBESITY RISK
Silverman et al. Diabetes Care 1998;21:B142-9; Hamilton et al 2010 Obesity (18):340-346 16
GDM
fetal hyper-
insulinemia
adipogenesis
BUT WHAT ABOUT THE BRAIN?
1. Altered leptin & insulin signaling
2. Placenta ‘trapping’: DHA suppletion
during pregnancy is not effective
3. Reduced DHA status at birth
4. Increased risk of cognitive deficits
EARLY LIFE DIETARY LIPID QUALITY: KEY MESSAGING
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▪ Dietary intakes of vegetables, EFA (n-3 fatty acids), iron, vitamin D and iodine are low; in contrast those of protein, saturated fatty acids and added sugar are high
▪ Poor maternal health and dietary gaps affecting postnatal infant growth impact not only physical growth & body composition but also (functional) brain development
▪ Dietary lipids provide the main building blocks AND affect functional development of the brain
▪ Increased supply of n3 DHA as well as reduced levels of dietary n6 LA
✓ improve brain membrane composition
✓ reduce obesity susceptibility (improve immune development)
✓ alter the neural circuit for satiety regulation
✓ prevent ELS induced cognitive impairments
▪ Challenged maternal health (obesity, GDM) impacts brain functional
development and may require a different dietary approach