1. Functional Foods and Nutrition Research 14th October 2014 Mary E Penny Instituto de Investigacion Nutricional

2. Big Business and increasing

3. Definition of Functional Foods Food with added health benefits beyond the usual nutritional value No single agreed definition Usually excludes “supplements”

4. Food Innate health benefits “Natural” without modification Examples: Quinoa (fiber and antioxidants) Liver (vitamin A) Orange juice (vitamin C) Enhanced Examples: Natural Potatoes selected for high iron content Bioengineered Golden 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?

5. “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 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

6. Examples of Categories: Institute of Food Technologists

7. 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 Health Claims Process 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

8. 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).

9. 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

10. 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 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

11. How can research help define health claims?

12. 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 defined Mechanism of action useful but not essential Stability, Interactions For instance a food with added mineral might be eaten with high fiber or phytate foods lowering bioavailability. Breastmilk Organoleptic properties Multimicronutrients, 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

13. 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 foodConsumption/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 responders Physical activity level Appropriate controls Study Design

14. Design of a study to assess a Functional Food Functional foodConsumption/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

15. Design of a study to assess a Functional Food Functional foodConsumption/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 Outcomes Claims should take into account the totality of of the data Study Design

16. 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 Food Eur J Nutr 2009; 48 Suppl 1:S23-S26

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

18. 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 Cons Allows meta-analysis and prevents publication bias – Patenting issues

19. 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!

20. 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

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

22. Mind-Map Of Study Design Hendriks H and Welch R. Beyond PASSCLAIM. 2010 – ILSI Europe report series

23. Summary Mind-map - Preparations

24. Summary - Mind-map: More thoughts on design

25. Gracias