Division of Human Nutrition WUR State of the Art – and Work in Progress!

WU Alumni Oost

Edith Feskens

What is ‘Nutrition’?

Food (voedsel)

Nutrition (voeding)

Health

Google Search: Gezonde Voeding

Wat is gezond?

Feiten en Fabels in de Media!

Feit: Fritessaus bevat minder kcal dan mayonaise.

Fabel: Een blokje kaas is gezonder dan een

bitterbal.

Feit: Vezels zet de darmen in werking en zorgen

voor een goede darmpassage.

Fabel: Suikervrij snoep bevat geen calorieën

Feit: Spiermassa verbruikt meer energie dan

vetmassa in het lichaam.

Fabel: Ik ben zwaarder omdat ik zware botten

heb.

Voedingsonderzoek is moeilijk (ivt Farma)

Het gaat niet om 1 stof maar om meerdere stoffen tegelijk.

De nutrienten en bio-actieve stoffen werken samen, of juist niet.

De nutrienten en bio-actieve stoffen werken op allerlei plaatsen in het lichaam, niet alleen op 1 orgaan.

Voedingsonderzoek is moeilijk: bewijslast

Experimenten versus Observaties

We kunnen niet eenvoudig experimenteren met voeding en chronische ziekten zoals kanker en HVZ…

Daarom bestuderen we het Natuurlijk Beloop in zgn Cohort Onderzoeken:

Relatieve Risico:: 3/5 1/5

Kenmerken Cohort onderzoek:

Prospectief, dus oorzaak gaat vooraf aan het gevolg

Maar mensen die meer roken hebben ook andere karakteristieken (mannen, dunner, meer alcohol, koffie..) = confounding (verstoring)

Bij Groente/Fruit mensen vaak gezondere eetgewoonten, meer lichamelijke activiteit…

Oplossing: statistische correcties

Let op: hoe goed is de voedingsinname gemeten?

Voedingsonderzoek is moeilijk: bewijslast

Voorbeeld van RCTs: parallel en cross-over

RCT: de controlegroep

Waarom is een controlegroep nodig?

Wat zou er gebeurt zijn zonder de interventie?

Oplossing een controlegroep, of een controlebehandeling: een behandeling met een bekend effect, of inactief (moet hetzelfde eruit zien, zgn. placebo)

RCT: de vergelijking

Beste vergelijking door:

● Random mensen toedelen aan behandeling/controle

● Zorgt voor gelijke verdeling risicofactoren

● Blinderen van onderzoeksmederwerkers (objectief!)

● Blinderen van deelnemers (even grote ‘placebo’ effecten)

● Dan is verschil in uitkomst tussen beide groepen toe te schrijven aan de behandeling (simpele data-analyse)

Kortom:

RCTs staan aan de top van de bewijslastpyramide

Maar voor voeding is een echte RCT lastig!

Dus… observationeel onderzoek ook belangrijk

Dus… meer tegenstrijdige resultaten

Dus… verwarring bij pers en consument

Nog meer lastige zaken: dosis

Human Nutrition in Wageningen

Campus Wageningen UR

Division AFSG

Division of Human Nutrition

190 people involved in research and education

40 scientific staff members involved in teaching

20 postdocs, researchers

45 technical assistants, dieticians, administrative staff

85 PhD fellows (~30% international, external)

764 students Nutrition & Health

448 BSc, 316 MSc (26% international), 2150 Alumni

Courses, individual scientific work, internship in public/private organisation

In 2015: Distance learning MSc Nutritional & Public Health Epidemiology

Education: e-learning

Publications

“To improve human health through better

nutrition” – 5 Chairs Nutrition

Dr. Frans Kok, professor in Nutrition and Health, Head Division of Human Nutrition

Dr. Michael Muller, professor in Nutrition, Metabolism and Genomics

Dr. Pieter van ‘t Veer, professor in Nutrition and Epidemiology

Dr. Renger Witkamp, professor in Nutrition and Pharmacology

Dr. Kees de Graaf, professor in Sensory Science and Eating behavior

Endowed Professors

Dr. Lisette de Groot Professor in Nutrition in the Elderly

Dr. Daan Kromhout Professor in Public Health Research / Vice- President the Netherlands Health Council

Dr. Michael Zimmermann Professor in Micronutrients and International Health

Dr. Ellen Kampman Professor in Nutrition and Cancer

Dr. Edith Feskens Professor in Nutrition and the Metabolic Syndrome

Dr. Hendriek Boshuizen Professor in Biostatistical Modelling for Nutritional Research

Dr Sander Kersten Professor in Molecular Nutrition

Research Strategy

Mechanistic studies

in vitro studies, animal experiments

Human studies

challenge studies, controlled trials

observational epidemiology

Cell Individual Population

Mission and Research strategy

Mission: “Improve health through better nutrition” Unique and complementary expertise's enable an integrated

multidisciplinary approach in education & research.

Determinants of food choice

Intake of foods and nutrients

Status and function

Health and disease

Cell, organ

Individual

Population

Two common research themes

International nutrition

To prevent deficiency and chronic disorders related to under- and over nutrition.

Metabolic health

To improve the ability to adapt to dietary challenges.

Nutrition and Health

Prof Frans Kok

International maternal & child nutrition Food-based approaches for prevention of deficiencies

Nutrition & ageing Nutritional strategies to optimize cognitive performance, muscle function in the elderly

Disease-related nutrition Dietary strategies to optimize nutrition status of patients

Nutrition, physical activity & sports Interaction and effect on performance and recovery

Bovine Colostrum Supplementation’s Lack of Effect on Immune Variables During Short-Term Intense Exercise in Well-Trained Athletes Carol, Witkamp, Wichers, Mensink

Nutrition and Health

Prof Frans Kok

International maternal & child nutrition Food-based approaches for prevention of deficiencies

Nutrition & ageing Nutritional strategies to optimise cognitive performance, muscle function In the elderly

Disease-related nutrition Dietary strategies to optimiseze nutrition status of patients

Nutrition, physical activity & sports Interaction and effect on performance and recovery

Nutrition and Health

Prof Frans Kok

International maternal & child nutrition Food-based approaches for prevention of deficiencies

Nutrition & ageing Nutritional strategies to optimise cognitive performance, muscle function in the elderly

Disease-related nutrition Dietary strategies to optimise nutrition status of patients

Nutrition, physical activity & sports Interaction and effect on performance and recovery

Nutrition and Health

International Nutrition

Instapa (EU-project) Novel staple-food based strategies to improve micronutrient malnutrition

Efficacy trial 300 rural Kenyan children, age 6-13 yrs. 18 wks. intervention 12 cassava varieties Carotenoid range: 700-1100 μg/100g Endpoint: serum retinol

Group 1= 35.3 (37.4) µg RAE Group 2= 45.9 (75.0) µg RAE Group 3= 211.6 (64.6) µg RAE*

Nutrition and Epidemiology

Prof Pieter van ‘t Veer

Etiological research:

Metabolic syndrome, Diabetes, Cardiovascular disease, including BP, Cancer (e.g. colon, breast)

Public health:

Risk groups and requirements, Prevention of diet-related non- communicable disease/ community based interventions

Biostatistics:

Evaluation dietary assessment methods, Meta-analysis methods Modelling of scenarios preventive strategies

Nutrition and Epidemiology

Prof Pieter van ‘t Veer

Etiological research:

Metabolic syndrome, Diabetes, - Cardiovascular disease, including BP, Cancer (e.g. colon, breast)

Public health:

Risk groups and requirements, Prevention of diet-related non- communicable disease/ community based interventions

Biostatistics:

Evaluation dietary assessment methods, Meta-analysis methods Modelling of scenarios preventive strategies

Dullemeijer et al.

Iron

Zinc

Folate

Vitamin B12

Iodine

Critical Reviews in Food Science and Nutrition, Volume 53, Issue 10, 2013, Special Issue:EURRECA. Dhonukshe-Rutten et al

Nutrition, Metabolism and Genomics

Prof Michael Müller

Molecular nutrition of fatty acid sensing Impact of sensing on glucose and lipid homeostasis

Metabolic Health

Flexibility of organs on cellular, functional level using phenotyping and challenge tests

Intestine as Gatekeeper

Integration of the effects of nutrients on the immune-metabolic function Immuno metabolism Impact of chronic metabolic, proinflamatory stress on organs (liver, adipose tissue) Role of Epigenetics in Ageing Long-term effects of nutrients, food patterns

Phenotyping the effect of diet on non-alcoholic fatty liver

disease. J Hepatol. 2012. de Wit, Afman, Mensink, Muller.

Overexpression of angiopoietin-like protein 4 protects

against atherosclerosis development. Arterioscler Thromb

Vasc Biol. 2013. Georgiadi, Stienstra, Kersten

Nutrition, Metabolism and Genomics

Prof Michael Müller

Molecular nutrition of fatty acid sensing Impact of sensing on glucose and lipid homeostasis

Metabolic Health

Flexibility of organs on cellular, functional level using phenotyping and challenge tests

Intestine as Gatekeeper

Integration of the effects of nutrients on the immune-metabolic function Immunometabolism Impact of chronic metabolic, proinflamatory stress on organs (liver, adipose tissue) Role of Epigenetics in Ageing Long-term effects of nutrients, food patterns

BODY FAT DISTRIBUTION

Subcutaneous fat vs. Visceral fat

ABDOMINAL OBESITY

Increased disease risk: T2DM, NAFLD, CVD

METABOLIC HEALTH

How to define metabolic health?

How to create a complete overview of personal

metabolic functioning (metabolic phenotyping)?

How to improve metabolic health with nutritional

interventions?

Nutrition, Metabolism and Genomics

Metabolic Health

The Belly Fat Study

Phenotyping of

84 individuals with

abdominal obesity

and high levels of

hepatic fat

Before and after a

lifestyle intervention:

Two different caloric-

restricted diets

Sensory Science & Eating Behaviour

Prof Prof Kees de Graaf

Effect of chemical properties on sensory perception & preference Role of texture and oral processing

Impact of sensory/metabolic signals on health and well-being Fibres, oral and gastric contributions to satiety, but-brain axis, energy sensing on tongue, in stomach

Psychobiology of reward Effects of taste and odour on eating behaviour, underlying mechanism

Effects of external signals Environment, information package on behaviour, intake and satiety

Sensory Science & Eating Behaviour

Prof Prof Kees de Graaf

Effect of chemical properties on sensory perception & preference Role of texture and oral processing

Impact of sensory/metabolic signals on health and well-being Fibres, oral and gastric contributions to satiety, but-brain axis, energy sensing on tongue, in stomach

Psychobiology of reward Effects of taste and odour on eating behaviour, underlying mechanism

Effects of external signals Environment, information package on behaviour, intake and satiety

Student project:

Question: Is bite frequency influenced

by the bite frequency of an eating

companion?

Methods: 33 young adults, couples

same sex had three warm meals

together, confederate was signaled to

eat at predetermined bite

frequencies.

Result: Bite frequency remained the

same within participants, while intake

did change.

Nutrition and Pharmacology

Prof Renger Witkamp

Kinetics & effects of bioactive lipids Endocannabinoids, related N-acylamines, mechanistic effects on eating behaviour and nutritional health

Metabolism in patients Strategies to optimize nutritional health (i.e. muscle preservation) by targeted food

Drug-nutrient interactions Investigate and predict the effects of multiple drugs on nutrient status

Measurement of Palmitoylethanolamide and Other N-Acylethanolamines During Physiological and Pathological Conditions. Balvers, Verhoeckx, Meijerink, Wortelboer and Witkamp

Nutrition and Pharmacology

Prof Renger Witkamp

Kinetics & effects of bioactive lipids Endocannabinoids, related N-acylamines, mechanistic effects on eating behaviour and nutritional health

Metabolism in patients Strategies to optimize nutritional health (i.e. muscle preservation) by targeted food

Drug-nutrient interactions Investigate and predict the effects of multiple drugs on nutrient status

Cross sectional studie 25(OH)D 13 drug groups – vitamin D levels, drugs relevant for elderly, ≥ 55 y, n = 870, hospitalized

Facilities

The new population based studies:

EetMeetWeet and NQplus

EMW: a sampling frame of 50,000 people of the area Wageningen-Food Valley-Gelderland

NQplus (Nutrition Questionnaires plus..)

detailed longitudinal study of 1750 EMW people (20-70 yrs)

Goals

Setting up an infrastructure for

● Methods to improve food consumption studies

● Association between diet and health markers

● Make link with eating behaviour, not only food and nutrient intake

● Metabolomics, nutrigenetics

● Sampling frame for sub-studies

● Microbiota

● MRI scan (body fat depots, arteries, brain)

● Transcriptomics (fat biopsies)

● etcetc

Questionnaires – all done by internet!

Determinants of dietary intake

demographic

social context

psychological factors

Determinants of Obesity

physical activity

sleep etc

Health and Well-being

Physical examination

a.o. DEXA

Physical examination

AGE-reader

Blood pressure and arterial stiffness

Biobank

TOFIs: Thin

outside, Fat Inside…

• Three men

• Same BMI = 24 kg/m2

• Waist from low to higher

• Intra-abdominal fat higher

More TOFIs

• Three men

• Waist same, 84 cm

• BMI bit lower

• IAAT much higher

Waist circumference

High risk diabetes and cardiovascular disease:

Men ≥102 cm

Women ≥ 88 cm

Or Waist-to-height ratio > 0.6

55

Effects of a Mediterranean diet

Knoops ea JAMA 2004: MediDiet and

Mortality:

Study design; Randomized controlled feeding

study

Subjects

Men and women

Abdominal obesity (Women >80 cm, Men >94 cm, or BMI >25 kg/m2)

40-65 y

Without diabetes mellitus

No use of anti hypertensives or cholesterol lowering medication

Outcome variables

Total cholesterol, HDL, LDL

Insulin, HOMA-IR, c-peptides

Hyperinsulinemic euglycemic clamp (subgroup)

2003B068

Study design: Completely controlled feeding trial

90% of daily energy needs were provided

Weight stable

3 Intervention diets

High SFA-diet ; Western diet

High MUFA-diet; SFA ,MUFA

Mediterranean diet; SFA ,MUFA

• More fruit and vegetables, Whole grain products

• Legumes; Nuts

• Fish; Red wine

2003B068

Study design

Run-in

(high-SFA)

High SFA-diet (n=20)

High MUFA-diet (n=20)

Mediterranean diet (n=20)

2 weeks 8 weeks

2003B068

Results; Serum lipids after 8-w of intervention

2003B068

Mean (sd)

High SFA-diet

(n=19)

High MUFA-

diet (n=18)

Mediterranean

diet

(n=20)

Total

Cholesterol

mmol/L

5.61 (1.15) 5.33 (0.69) 5.11 (1.00)

LDL-cholesterol

mmol/L 3.97 (1.03) 3.55 (0.66) 3.32 (0.85)

HDL-cholesterol

mmol/L 1.26 (0.24) 1.35 (0.38) 1.39 (0.48)

P<0.05

60

Effects of a Mediterranean diet

Run-in

(high-SFA)

High SFA-diet (n=20)

High MUFA-diet (n=20)

Mediterranean diet (n=20)

2 weeks 8 weeks

-0,8

-0,7

-0,6

-0,5

-0,4

-0,3

-0,2

-0,1

0

SFA

MUFA

Medi

TotC/HDL-c Apo-B / Apo-AI

* ** * * 4.58

4.27

3.88

1.06

0.990.94

Knoops ea JAMA 2004: MediDiet and

Mortality:

Bos ea, van Dijk ea :MARIS trial

61

Effects of a Mediterranean diet

Run-in

(high-SFA)

High SFA-diet (n=20)

High MUFA-diet (n=20)

Mediterranean diet (n=20)

2 weeks 8 weeks

Knoops ea JAMA 2004: MediDiet and

Mortality:

Bos ea, van Dijk ea :MARIS trial

Gene expression results Maris

62 Van Dijk ea AJCN 2009

Beneficial effects of the Mediterranean diet by ..

Olive oil or vegetable oil?

Fruit and vegetables?

Fish, nuts?

Low glycemic index?

Whole grains?

Alcohol, red wine, polyphenols?

A combination of the above…..?