Functional Foods and Nutrition Research

14th October 2014

Mary E Penny

Instituto de Investigacion Nutricional

Big Business and increasing

Definition of Functional Foods

Food with added health benefits beyond the usual nutritional value

No single agreed definitionUsually excludes “supplements”

FoodInnate health benefits

“Natural” without modification

Examples:

•Quinoa (fiber and antioxidants)

•Liver (vitamin A)

•Orange juice (vitamin C)

Enhanced

Examples:

•NaturalPotatoes selected for high iron content

•BioengineeredGolden rice (Vitamin A)

Food with added/altered substance

Reduction of ingredient Example:

Low fat milk

Added ingredient: Examples:

Fermenting bacteria (yogurt)

Milk with added Vitamin D/iron/zinc

Spread with added phytosterol

or

May involve more than one change

What are Functional Foods?

“Functional” maybe a property of a whole type of food

Fruits and vegetables

Whole Grains

Property of a specific “ingredient “ of the food

Foods and Food components

Fiber,Vitamin A

ZincAntioxidant

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

Functional Food Task Force of International Life Sciences Institute (Europe) ILSI EuropeInitiated 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

Health ClaimsProcess for the assessment of Scientific support for claims on food

(PASSCLAIM – 2007) Beyond PASSCLAIM – New Guidance (2009)

Japan leader in Functional foods 1980s “Foods for specialized health use”

Purpose: Food products eligible for

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

Reduction of specific illness or deficiency –

disease risk

Maintenance of health (Enhanced

function)

Treatment or management of

illness

Gastrointestinal health

The gut microbiome

Linear growth in infancy

Antioxidants – effects on ageing

Improved sports performance

Mental health – memory

Calcium - osteoporosis

Vitamin A – night blindness

N-3 PUFA – Cardiovascular risk

Folic acid – Spina bifida

Low fat – overweight

Gluten free – celiacs

Low glycemic index – Diabetes M

European commision: Functional foods 2010

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 foodConsiders safety and scientific validity of claims about foods – doesn´t specify “Functional foods”Same framework as conventional foods

2009 ILSI workshop

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?

Design of a study to assess Functional Foods and their components

Functional food Consumption/Intake (Bio) markers Health change(Health outcome)

Food or food component should be characterized.Minumal dose definedMechanism of action useful but not essential

Stability,

InteractionsFor instance a food with added mineral might be eaten with high fiber or phytate foods lowering bioavailability. Breastmilk

Organoleptic propertiesMultimicronutrients, Fish

Safety

Should comply with existing regulation

How will cooking affect it – example DHA and high temperature cooking

How will storage affect it?

Study Design

Target population : who do we want to benefit

Study group must be representative of target groupAgeCultural considerations/socio-economicDietary practices/mores

Functional food Consumption/Intake (Bio) markers Health change(Health outcome)

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,

Healthy vs “not healthy”Low, normal and High respondersPhysical activity levelAppropriate controls

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 consumptionAdequate duration and follow-upFood matrix and dietary context

Monitoring of compliance

Study Design

Design of a study to assess a Functional Food

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 groupShould change in statistically significant way

Outcomes

Claims should take into account the totality of of the data

Study Design

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

Reduced risk of disease

ENHANCED FUNCTION CLAIMS

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 FoodEur J Nutr 2009; 48 Suppl 1:S23-S26

Intermediate measurements: Markers

Biological function: Bacterial populations in the gut (probiotics)

Key stage in disease development: Bone densityFlow mediated dilatation for CVD

Antioxidant measure

Glycemic index

Hemoglobin

Satiety-consumption

Muscle strength

Lipid profile

Markers

Nutrigenomics: Changes in gene expression as a result of dietary nutrients

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

Adverse events

Registration of trials: Pros and ConsAllows 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

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

Randomized controlled Trials

Political/regulatory aspects in the countryWhat are the local regulations about food additives?,Human studies and clinical trial regulations?

Dietary Reference Intakes needed for a wider range of nutrients

Discussion about “Qualified health claims: “may be beneficial”Differences between countries USA, Japan, EU

Other considerations

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