Functional Foods and Nutrition Research

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

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. What are Functional Foods? Food Innatehealthbenefits Food withadded/alteredsubstance or • “Natural” • withoutmodification • Examples: • Quinoa (fiber and antioxidants) • Liver (vitamin A) • Orange juice (vitamin C) • Enhanced • Examples: • Natural • Potatoesselectedforhighironcontent • Bioengineered • Golden rice (Vitamin A) Reduction of ingredient Example: Lowfatmilk Added ingredient: Examples: Fermenting bacteria (yogurt) Milkwithadded Vitamin D/iron/zinc Spread withaddedphytosterol May involve more than one change

5. Foods and Food components Property of a specific “ingredient “ of the food “Functional” maybe a property of a whole type of food Fruits and vegetables Whole Grains 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. 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

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 Maintenance of health (Enhanced function) Reduction of specific illness or deficiency – disease risk 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. 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” • Notaneasytask: • Riskassessment – safety • Changingpriorities in health – epidemic of non communicablediseases • Context of therest of thediet • Variabilityacrossconsumers • Links betweendiet and healthnotalwaysknown 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

11. How can research help define health claims?

12. Study Design Design of a study to assess Functional Foods and their components Foodorfoodcomponentshould be characterized. Minumaldosedefined Mechanism of actionusefulbutnotessential Healthchange (Healthoutcome) Functionalfood Consumption/Intake (Bio) markers Shouldcomplywithexistingregulation Safety Stability, Interactions Forinstance a foodwithadded mineral mightbeeatenwithhighfiberorphytatefoodsloweringbioavailability. Breastmilk Howwillcookingaffectit – example DHA and hightemperaturecooking Howwillstorageaffectit? Organolepticproperties Multimicronutrients, Fish

13. Study Design Target population: who do wewanttobenefit Studygroupmustberepresentative of target group Age Cultural considerations/socio-economic Dietarypractices/mores Healthchange (Healthoutcome) Functionalfood Consumption/Intake (Bio) markers Healthy vs “nothealthy” Low, normal and High responders Physicalactivitylevel Appropriatecontrols 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,

14. Study Design Design of a study to assess a Functional Food Healthchange (Healthoutcome) Functionalfood Consumption/Intake (Bio) markers Dose/amountshouldbeconsistentwith normal consumption Adequateduration and follow-up Foodmatrix and dietarycontext Monitoring of compliance

15. Study Design Design of a study to assess a Functional Food Outcomes Healthchange (Healthoutcome) Intermediateoutcome – how can itbemeasured? Definitiveoutcome (Endpoints) How can itbemeasured? Endpointsmaybedifficulttomeasure, long time Markers are oftenneeded/used Shouldbebiologicallyvalid (Knownrelationshipwiththeoutcome) Knownvariabilityamong target group Shouldchange in statisticallysignificantway Functionalfood Consumption/Intake (Bio) markers Claimsshouldtakeintoaccountthetotality of ofthe data

16. Markers of Exposure to functional food component Markers of target function/ biological response Consumption of functional food component Markers of intermediate endpoint Reduced risk of disease Enhanced target function REDUCTION OF DISEASE RISK CLAIMS ENHANCED FUNCTION 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. Markers Intermediatemeasurements: Markers Biologicalfunction: Bacterialpopulations in thegut (probiotics) Key stage in diseasedevelopment: Bonedensity Flowmediateddilatationfor CVD Antioxidantmeasure Glycemicindex Hemoglobin Satiety-consumption Musclestrength Lipidprofile Nutrigenomics: Changes in gene expression as a result of dietary nutrients

18. 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

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 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

21. 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

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