PHENOTYPIC FLEXIBILITY AS A NEW WAY TO QUANTIFY EFFECTS OF Suzan Wopereis

PHENOTYPIC FLEXIBILITY AS A NEW
WAY TO QUANTIFY EFFECTS OF
FOOD AND NUTRITION ON HEALTH
Suzan Wopereis
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Why is it so difficult to show an health effect in nutrition intervention trials?
Subtle and longterm effects
Target population
is healthy
Interactions between
ingredients/nutrients
Multiple
mechanisms
Multiple target
tissues
Interindividual
variation
Choice of
reference
Health = ?
Huber et al., BMJ 2011:
Two research-projects related to flexibility
1. PhenFlex
Innovative and ground-breaking research to phenotypic flexibility as
a new way to quantify effects of food and nutrition on health
2. Whole grain resilience
Application of phenotypic flexibility to deliver proof of concept that
phenotypic flexibility can substantiate health benefits of whole wheat
products
PhenFlex
Innovative scientific approach that aims to develop methods and tools to
substantiate subtle effects of food and nutrition on health (in healthy
subjects!)
An approach that measures health instead of disease
Based on:
1. New definition of health
2. System biology based biomarkers
3. Challenge test to determine resilience
The ‘challenge concept’
Healthy situation:
Too high
Too low
The ‘challenge concept’
Unhealthy
PhenFlex
challenge
Healthy
PhenFlex
challenge
‘PhenFlex challenge’: 75g glucose, 60g fat, 20g protein
OPGTT
Extensive analyses
Time course studies:
Blood sampling at multiple time points after challenge,
up to 10 hours
metabolome
proteome
clinical chemistry
transcriptome
Aim: to monitor response of multiple biological processes
Biomarkers of health:
• Challenge response
• Difference “healthy” vs “T2D”
 Reduced adaptability study
Healthy subjects
hrs
PhenFlex
challenge
Subjects with
type-2 diabetes
hrs
PhenFlex
challenge
Summary
Only baseline effect
PhenFlex challenge effect
Blunted lipolysis
Blunted energy metabolism
↑ liver damage
hypertriglyceridemia
Biomarkers of health:
• Variation in response within 100 healthy subjects
with different phenotypic flexibility
 Healthy ranges study
hrs
PhenFlex
challenge
20-29
L-N
30-59 30-59 30-59
Low Normal High
60-70
N-H
hrs
PhenFlex
challenge
Variation in phenotypic flexibility
in healthy subjects
60-70
N-H
stress
lipids
20-29
L-N
Based on ~160 markers
Variation in phenotypic flexibility
in healthy subjects
Age 30-59
LOW FAT%
stress
lipids
Based on ~160 markers
Variation in phenotypic flexibility
in healthy subjects
Age 30-59
LOW FAT%
NORMAL FAT%
stress
lipids
Based on ~160 markers
Variation in phenotypic flexibility
in healthy subjects
Age 30-59
LOW FAT%
NORMAL FAT%
HIGH FAT%
stress
lipids
Based on ~160 markers
Low education shows higher score on Flex-index
hrs
Flex-index
hrs
Education level
Higher hours of sleep shows higher score on Flex-index
hrs
Flex-index
hrs
hours of sleep
Especially in persons that report on sleeping problems…
hrs
Flex-index
hrs
hours of sleep
The phenotypic flexibility
health space
Age 30-59
LOW FAT%
NORMAL FAT%
HIGH FAT%
stress
lipids
Subject S052
Age: 59
Fat: 21.4% (=Low)
Metabolic age > 80!
Diagnosis:
• Induced liver stress:
ALAT, GGT, Fisher
• Reduced lipid handling:
TG, NEFA, cholesterol
• Insulin resistant:
↓Matsuda, ↑HOMA, ↑glucose, ↑insulin, ↑C-peptide
• Induced muscle stress:
Creatinin, prot deficiency, 3-methylhistidine
From Phase 1….
Biomarkers of health:
• Challenge response
• Difference healthy vs T2D
Biomarkers of health:
• Variation in response within 100
healthy subjects with different
phenotypic flexibility
Reduced adaptability study
Healthy ranges study
….into Phase 2
INTERVENTION STUDY
Proof of concept that new biomarkers of health are useful to
substantiate beneficial health effects in a dietary intervention study
New partners welcome to join !
Whole grain resilience:
towards health claim substantiation for whole wheat products
Human study
Randomised, double blind, placebo controlled, including challenge test
Group A: whole grain wheat
12 weeks
Group B: No whole grain wheat
Use of self-measuring
devices
Take home message
For substantiation of health benefits of nutrition we need biomarkers
of health rather than biomarkers of disease
These are “multi-biomarker” panels representing defined and
accepted health-related processes
In combination with the new PhenFlex challenge test most defined
health related processes are modulated
In this way we believe to be able to measure health effects of nutrition
In 2020: New book
releases with
scientific health
facts?
Acknowledgements
Ben van Ommen
Sabina Bijlsma
Gertruud Bakker
Tim van den Broek
Annette Stafleu
Wilrike Pasman
Annelies Dijk-Stroeve
Andre Boorsma
Herman van Wietmarschen
Marjan van Erk
Nard Clabbers
Jan Willem van der Kamp
Carina de Jong
and many others…
THANK YOU FOR
YOUR ATTENTION