Download Design of a study to assess a Functional Food

Functional Foods and
Nutrition Research
Mary E Penny
Instituto de Investigacion Nutricional
14th October 2014
Big Business and increasing
Definition of Functional Foods
Food with added health benefits
beyond the usual nutritional value
No single agreed definition
Usually excludes “supplements”
What are Functional Foods?
Food
Innate health benefits
“Natural”
or
Enhanced
Reduction of
ingredient
Added
ingredient:
Examples:
Example:
Examples:
• Natural
Potatoes selected for
high iron content
Low fat milk
Fermenting bacteria
(yogurt)
without modification
Examples:
• Quinoa (fiber and
antioxidants)
• Liver (vitamin A)
Food
with added/altered substance
• Bioengineered
Golden rice (Vitamin A)
Milk with added
Vitamin D/iron/zinc
Spread with added
phytosterol
• Orange juice (vitamin C)
May involve more than one change
Foods and Food components
“Functional” maybe a property of a
whole type of food
Fruits and vegetables
Whole Grains
Property of a specific
“ingredient “ of the food
Fiber,
Vitamin A
Zinc
Antioxidant
Protein
With increasing interest in “Health” benefits of food there came an
increasing tendency to make health claims for foods and so a need for
definitions and regulations especially for Foods that have been modified
Examples of Categories: Institute of Food Technologists
Japan leader in Functional foods 1980s “Foods for specialized health use”
Functional Food Task Force of International Life Sciences Institute (Europe) ILSI Europe
Initiated a “concerted action project” in 2001 FUFUSE (Functional food science in Europe)
EU - Foods with scientifically substantiated benefits
for health and/or performance above normal
nutritional functions
Purpose: Food products eligible for
Health Claims
Process for the assessment of Scientific support for claims on food
(PASSCLAIM – 2007)
Beyond PASSCLAIM – New Guidance (2009)
ILSI Europe: Beyond PASSCLAIM 2010
The EU Concerted Action - Two types of health claims relevant to functional foods,
must always be valid in the context of the whole diet and must relate to the amounts of
foods normally consumed.
These are:
1. TYPE A: "Enhanced function"claims that refer to specific physiological, psychological
functions and biological activities beyond their established role in growth, development
and other normal functions of the body.
This type of claim makes no reference to a disease or a pathological state, e.g. certain
non-digestible oligosaccharides improve the growth of a specific bacterial flora in the gut;
caffeine can improve cognitive performance.
2. TYPE B "Reduction of disease-risk "claims that relate to the consumption of a food or
food component that might help reduce the risk of a specific disease or condition because
of specific nutrients or non-nutrients contained within it (e.g. folate can reduce a woman's
risk of having a child with neural tube defects, and sufficient calcium intake may help to
reduce the risk of osteoporosis in later life).
Possible health benefits
Maintenance of
health (Enhanced
function)
Reduction of specific
illness or deficiency –
disease risk
Treatment or
management of
illness
Gastrointestinal health
Calcium - osteoporosis
Low fat – overweight
The gut microbiome
Vitamin A – night blindness
Gluten free – celiacs
Linear growth in infancy
N-3 PUFA – Cardiovascular risk
Low glycemic index – Diabetes M
Antioxidants – effects on ageing
Folic acid – Spina bifida
Improved sports performance
Mental health – memory
European commision: Functional foods 2010
2009 ILSI workshop
Objective of the workshop was to provide guidance to
substantiate health claims on foods
Food producers, manufacturers, regulators, public needed to know
the the evidence on which claims could be made, the basis for
claims and the process of regulating claims – note that the concern
was to regulate “claims” not “food”
Not an easy task:
•
•
•
•
•
Risk assessment – safety
Changing priorities in health – epidemic of non communicable diseases
Context of the rest of the diet
Variability across consumers
Links between diet and health not always known
CODEX – Alimentaria provides international regulations and standards with regard to food
Considers safety and scientific validity of claims about foods – doesn´t specify “Functional foods”
Same framework as conventional foods
Lupton JR. Scientific substantiation of claims in the USA: focus on functional foods. Eur J Nutr 2009;48 (suppl 1):S27-S31
How can research help define health claims?
Study Design
Design of a study to assess Functional Foods and their components
Functional food
Consumption/Intake
(Bio) markers
Food or food component should be characterized.
Minumal dose defined
Mechanism of action useful but not essential
Should comply with existing regulation
Safety
Stability,
Interactions
For instance a food with added mineral might be eaten with high fiber or phytate
foods lowering bioavailability. Breastmilk
How will cooking affect it – example DHA and high temperature cooking
How will storage affect it?
Organoleptic properties
Multimicronutrients, Fish
Health change
(Health outcome)
Study Design
Target population : who do we want to benefit
Study group must be representative of target group
Age
Cultural considerations/socio-economic
Dietary practices/mores
Functional food
Consumption/Intake
(Bio) markers
Health change
(Health outcome)
Healthy vs “not healthy”
Low, normal and High responders
Physical activity level
Appropriate controls
Example : Cereal with Probiotic to reduce diarrhea would need to be targetted at children 0-2
years, population with high diarrhea rates, eating cereal paps,
Study Design
Design of a study to assess a Functional Food
Functional food
Consumption/Intake
(Bio) markers
Health change
(Health outcome)
Dose/amount should be consistent with normal consumption
Adequate duration and follow-up
Food matrix and dietary context
Monitoring of compliance
Study Design
Design of a study to assess a Functional Food
Outcomes
Functional food
Consumption/Intake
(Bio) markers
Health change
(Health outcome)
Intermediate outcome – how can it be measured?
Definitive outcome (Endpoints) How can it be measured?
Endpoints maybe difficult to measure, long time
Markers are often needed/used
Should be biologically valid (Known relationship with the outcome)
Known variability among target group
Should change in statistically significant way
Claims should take into account the totality of of the data
Consumption
of functional
food
component
Markers of
Exposure to
functional
food
component
Markers of
target
function/
biological
response
Markers of
intermediate
endpoint
Enhanced
target
function
ENHANCED
FUNCTION CLAIMS
Reduced
risk of
disease
REDUCTION OF
DISEASE RISK
CLAIMS
The FUFOSE strategic scenario of markers for use in the scientific support of claims for foods
Agget PJ The Process of Assessment of Scientific Support for Claims on Food
Eur J Nutr 2009; 48 Suppl 1:S23-S26
Markers
Intermediate measurements: Markers
Biological function: Bacterial populations in the gut (probiotics)
Key stage in disease development:
Bone density
Flow mediated dilatation for CVD
Antioxidant measure
Glycemic index
Hemoglobin
Satiety-consumption
Muscle strength
Lipid profile
Nutrigenomics: Changes in gene
expression as a result of dietary
nutrients
Adverse events
Adverse Event reporting
Other names: Co-effects, Co-events, side effects
Events will always occur, complaints cannot be avoided
But important to record, for safety monitoring, ethics,
and may be expected for publication
Registration of trials: Pros and Cons
Allows meta-analysis and prevents publication bias – Patenting issues
Types of studies
Animal studies provide information on mechanisms of action, biomarkers, potential
benefits
Longitudinal epidemiological observation studies in humans including detailed dietary
studies provide initial evidence eg Fruits and vegetables – but is it enough?
But trails will be needed for health claims
Single arm studies are not acceptable
Randomized control studies (Gold standard)
Cross over and parrallel designs
Longitudinal RCTs - depends on outcome
(prevention of anemia, increased sports performance relatively quick,
prevention of dementia long time)
Discussion about Pharmacological approach to Food trials - but evidence is needed!
Type of Studies
Randomized controlled Trials
 Population characteristics, numbers/sample size
 Consent process
 Inclusion and exclusion criteria/screening
 Randomization
 Delivery of food, direct observation, packaging, amounts,
measurement; surveillance
 Adverse effects surveillance
 Loss to follow-up
 Outcomes: Measurement of outcomes, duration
Other considerations
Discussion about “Qualified health claims: “may be beneficial”
Differences between countries USA, Japan, EU
Political/regulatory aspects in the country
What are the local regulations about food additives?,
Human studies and clinical trial regulations?
Dietary Reference Intakes needed for
a wider range of nutrients
Mind-Map Of Study Design
Hendriks H and Welch R. Beyond PASSCLAIM. 2010 – ILSI Europe report series
Summary Mind-map - Preparations
Summary - Mind-map: More thoughts on design
Gracias