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Véronique MAQUET – KitoZyme

A la rencontre des aliments fonctionnels : du développement à la mise sur le marché. Quels sont les défis à relever ?

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Aliments fonctionnels: du développement à la mise sur le marché, quels sont les défis à relever?

Véronique MAQUET

Product Development Manager and Regulatory Affairs

KitoZyme

March 27, 2012 Liège Créative

► FuFo definitions & generalities ► FuFo market ► FuFo opportunities and challenges ► Chitin-glucan: A case study

Agenda

CONFIDENTIAL - Copyright © July 2009 KitoZyme – All rights reserved 2

► No universally accepted (legal) definition for functional foods

A food can be regarded as ‘functional’ if it is satisfactorily demonstrated to affect beneficially one or more target functions in the body, beyond adequate nutritional effects, […] Functional foods must remain foods and they must demonstrate their effects in amounts that can normally be expected to be consumed in the diet […]

A functional food can be a natural food, a food to which a component has been added, or […] has been removed by technological or biotechnological means.

A functional food might be functional for all members of a population or for particular groups of the population […] Source: Diplock et al. (1999)

Foods and food components that provide a health benefit beyond basic nutrition […]

provide essential nutrients often beyond quantities necessary for normal maintenance, growth, and development, and/or other biologically active components that impart health benefits or desirable physiological effects. […] Source: Institute of Food Technologists

3 CONFIDENTIAL - Copyright © July 2009 KitoZyme – All rights reserved

How to define functional foods?

►  Conventional/natural foods with bioactive components ●  foods that contain inherent functional components (e.g., soy protein, cranberries)

►  food to which a component has been added = fortified or enhanced foods

●  foods that naturally provide a bioactive substance may be enhanced to increase the level present in the food (e.g., eggs with increased levels of omega-3 fatty acids)

= naturally enhanced functional food ●  alternately, foods that do not naturally contain a substance

can be fortified to provide consumers with a broader selection of food sources for a particular component and its health benefit (e.g., calcium-fortified orange juice).

►  health benefits for consumers may result from increasing the consumption of substances already part of an individual’s diet or from adding new substances to an individual’s diet.

Functional foods can take many forms

4

Traditional paradigm - Clear distinction between the use and purpose of foods vs. drugs

5

FOOD & food components DRUGS

►  Energy; nutrition, necessary for life; ►  increasing evidence for beneficial effects

beyond basic nutrition + reduction of risk disease

►  Treatment of disease, symptom or condition

►  No prescription or supervision needed, consumer selects

►  Prescribed by health care professionals

►  Sold in supermarkets, drugstores, online, major retailers

►  Sold in pharmacies, hospitals

►  Target function/biological response are multifaceted, many interactions

►  Clear target; cause & effect relationship

►  Safe ►  Clear doses (as prescribed by doctor) . ►  Benefit> risk

►  Missing prescription/accuracy of intake ►  Motivation to consume is much higher (e.g. need for ease of pain).

►  Health benefit of prevention is difficult perceive for the consumer *

►  Health effect is immediate

* But the role of food in PREVENTION is increasing

Some functional food components may improve memory, reduce arthritis, reduce cardiovascular disease and provide other benefits typically associated with drugs!

Source : adapted from Bröring

►  “food supplements are concentrated sources of nutrients or other substances with a nutritional or physiological effect whose purpose is to supplement the normal diet. They are marketed ‘in dose’ form i.e. as pills, tablets, capsules, liquids in measured doses etc.” (EC 2007).

►  dietary supplement : “a product taken by mouth that contains a ‘dietary ingredient’

intended to supplement the diet […] vitamins, minerals, herbs or other botanicals, amino acids, […] also extracts or concentrates, and may be found in many forms such as tablets, capsules, softgels, gelcaps, liquids, or powders (FDA 2007)

►  For nutraceuticals: the concept is less clear !!

► ALL CONTAIN one (or more) specific biologically active ingredients= FOOD INGREDIENT

Distinction between functional food and food/dietary supplement

6

►  Functional foods can co-exist with traditional medical approaches ●  Better consumer awareness of food impact on heath ●  Problems of actual healthcare system: expensive & time-

constrained ►  Functional foods fit into a continuum that ranges from health

maintenance/promotion to disease treatment

►  New functional foods will continue to expand the continuum, providing additional options for consumers.

Function food: a new paradigm


Source: IFT

► Health effects ► Sensory properties (e.g. taste, odor, texture) ► Processing functionalities (e.g. heat/chemical stability) ► Versatility , i.e. relevance for different indications and

markets ► Regulatory compliance : safety & efficacy ► Consumer relevance (e.g. awareness)

Properties of functional ingredients


► The 385 functional food products that were identified for the European market contained 503 different “functional” ingredients.

Diversity on functional food/funtional ingredients


Source: Stein et al, 2008

► The US functional foods market is estimated to be the largest in the world ($20-30 billion) (source: Nutrition Business Journal, S&P) accounting for 35-50 % of global sales.

► The top 20 FuFo companies account for ~ 70% of the US market

►  Asia-Pacific is the next biggest market. ► Together, the US and Asia-Pacific are estimated to account

for approximately three-quarters of the current global market for functional foods (source: Scientis Advisors )

► EU market range from EUR 6-20 billion ●  dairy products seem to have the biggest market share,

followed by beverages and then cereals, snack food and fats ●  168 EU companies active in the field of functional food (EC,

2008)

Functional food market


► Greater health awareness by consumers ●  European consumers only have limited knowledge about the

interaction of specific food components, nutrition and health.

► Demographics changes ► Potential for premium pricing ► Advance in food technology ► New evidence-based science linking diet to disease and

disease prevention ► New opportunities: Disease modifying nutrition ► Nutrigenomics (Personalized nutrition)

► Ex/ nutrition for the elderly

Growth drivers and success factors

11

Foods may be developed to promote the expression of specific metabolites, reducing or preventing common diseases that afflict consumers with a specific genotype. Consumers might select functional foods and tailor their diets to meet changing health goals and different requirements at different ages.

►  Products with an easy-to-feel effect (energy boost) ►  Innovative packaging, i.e. “daily-dose” packaging ►  New segments ►  Target a niche, communicating a specific health benefit linked to a common

aliment or incorporating multiple desirable qualities into a single product. ●  ex: Kraft, probiotic nutrition bar—shelf-stable (without the need for

refrigeration).

Growth drivers and success factors


►  In 2004 Nestlé declared it was “moving from an agrifood business to an R&D-driven nutrition, health and wellness company.” (SOURCE The economist) .

►  Other top food and beverage companies have signaled similar intentions, including Danone, Unilever, General Mills, Kellogg, PepsiCo, Coca-Cola, Yakult, and Kraft.

Industry dynamics

13 Source Pricewaterhouse Coopers, 2009

Key categories and emerging products in US


►  Top products: Beverages ●  Consumer preference for the convenience and versatility of beverages ,

ease of creating tasty products and innovative packaging

►  Top health benefit= energy drinks ●  Quick benefit feeling ●  Growth niches: certain kinds of energy drinks and isotonics (beverages

that replace lost electrolytes or rehydrate)

►  Top food categories : soft drinks and dairy products ●  Soft drinks incl. soft drinks, enhanced waters and others products

●  yogurts: awareness of helpful bacteria; single portion (DANONE!) ►  Categorization by age:

●  older consumers purchase products with effect on gut, bone, heart health

●  younger consumers prefer products with claim on weight management, mental faculties; infant health improvement

Key categories and emerging products in US


► Frequent approaches involved acquisitions, partnerships or licenses

Identifying opportunities: market entry strategies


Sources: Thomson Financial, Jefferies International, Nutraceuticals Wrold,Mergerarket, Dairyreporter. com

►  New disciplines that will contribute to the rapid development of functional foods. ●  Nutrigenomics or how dietary components affect the protein profile of an

individual ●  Proteomics or how that altered protein profile affects the biological systems

of the individual ●  Metabolomics that describes the cellular response to the changes.

►  New technologies to produce bioactive food components from non traditional sources. ●  Abbadi et al.(2004) developed transgenic plant oils enriched with very long

chain polyunsaturated fatty acids. ●  Canola seeds as a source for production of stearidonic acid (a precursor for

eicosapentaenoic acid) and omega-3 fatty acids in the diet (James et al., 2003; Ursin, 2003).

►  Emerging technologies in food processing ►  new methods for stabilizing ingredients, optimizing texture, improving

product taste.

Technological opportunities


►  In one study, 93% of consumers believed certain foods have health benefits that may reduce the risk of disease or other health concerns. In addition, 85% expressed interest in learning more about the health benefits offered by functional foods (Source: IFIC, 2002)

= logical extension of traditional nutritional interventions -> Needs changes in foods, food regulation & marketing:

paradigm shift

Consumer demands for functional foods


► Proven effect: substantiation, level of scientific evidence ●  Validate efficacy & establish appropriate dietary level ●  dose-response relationship, clinical outcomes and individual

variations in response. ●  precise understanding of the mechanisms of action for known

nutrients

► Technical challenges: ●  Extrapolation dose/day to dose/serving ●  Compatibility with food processing

Challenges – R&D


► Price positioning/sensitivity ►  Impact of claims on sales volumes (ex of Activia, Actimel

in UK, FR) ► Building awareness among consumers

Challenges – Marketing


► Regulatory policies must ensure the safety and efficacy of products and the accuracy of their marketing claims ●  establish safety ●  establish efficacy ●  establish appropriate dietary levels ●  protect consumers from false and misleading claims ●  need for harmonization

► Europe ●  Nutritional and HC claim Regulation (EC) 1924/2006 ●  EFSA scientific assessment

► US-FDA

Challenges – Regulatory


► Since Dec. 2006, nutrition and health claims are regulated according to Regulation (EC) 1924/2006 ●  applied to all food and beverages sold in EU ●  + foods for Particular Nutritional Uses (PARNUTS) and dietary

supplements ●  also to communication, advertising, promotions,…

► 3 types of claims ► Scientific assessment by EFSA ► Labelling ► Difficult approval/market authorization for novel

ingredient: long process (Novel Food: EC 258/1997) ► The functional foods currently available represent only a

fraction of the potential opportunities for consumers to manage health through diet.

Challenges – Regulatory


Health claims

Scope

Art. 13 13.1 Describe the role of a nutrient or other substance in (a) growth , development and the func>ons of the body; (b) psychological/behavior func>ons; (c)  slimming or weight control Generic claims via na>onal list consolidated by EC and MS (>4000 claims) Based on generally accepted scien>fic data

13.5 Based on emerging science and/or include a request for the protec>on of the proprietary data. Applied to all new func>onal claims not previously submiNed via the na>onal lists (MS)

Art. 14 Disease risk-‐reduc>on claims; claims related to children’s health & development

Challenges – Which Health Claims in Europe?

23

Refers to a normal function of the body or to a risk factor , without stating, suggesting or implying its reduction Ex: maintains [normal vital function of the body]

Refers to reduction of a risk factor of a disease, with or without mentioning the disease name Ex: lowers [risk factor]

A risk factor is a factor associated with the risk of a disease that may serve as a predictor of the development of that disease (EFSA)

Number of established risk factors is very limited !! Ex for coronary heart disease • Elevated blood LDL-chol, total chol, blood pressure • No need to show reduced incidence of the disease

Source: Cantox, EAS



►  Criteria for HC substantiation: 1.  The claim effect is beneficial for human health

o  Is the claimed effect a beneficial physiological effect? ●  e.g. Weight management- yes; satiety- might be

o  Is the claimed effect sufficiently defined? ●  E.g. transit time- yes (measurable by generally accepted

method) ; gut health – too general 2.  A cause and effect relationship is established between the consumption of

the food/constituent and the claimed effect in humans (for the target group under the proposed conditions of use)

3.  The quantity of food and the pattern of consumption required to obtain the effect could reasonably be achieved as part of a balanced diet

4.  The studies population is representative of the target population ►  Scientific substantiation ►  Scientific assessment should be of the highest possible standard and based

on the totality of evidence (= totality of available scientific data) and by weighing the evidence

►  Evidence should consist primarily of human studies

Source: Cantox



►  Requirements for a favorable EFSA scientific opinion : 1.  The food/food constituent has been sufficiently characterized

L Not for some botanicals, probiotics! 2.  The claimed effect is beneficial to the health of the general population

(beneficial physiological effect) L Not for balanced intestinal flora, increase in beneficial bacteria in the gut

3.  A cause and effect relationship has been demonstrated between consumption of the food/food constituent and the claimed effect (for the target group under the proposed conditions of uses)

some reasons for rejection: L the studied population was not relevant to the target population L the studied product/dose was not specific to the target product/dose was not relevant to the target population

L studies submitted were of poor methodological quality and could not be used to establish cause & effect

►  EFSA is applying a high scientific bar for the scientific substantiation of all HC

Source: Cantox

Qualified Health Claims vs. Structure/Function Claims

Challenges – Which Health Claims in US?


► Structure/Function Claims ●  describes the effect of a nutrient or ingredient on normal

structure or function – includes “maintaining” such structure or function, or preventing a nutrient deficiency disease

●  ex: “Calcium builds strong bones”; “Helps support a healthy immune system “

●  for labeling of dietary supplements and conventional food ●  FDA does not conduct scientific review of S/F claims ●  do not require approval ●  no specification on the scientific evidence required (e.g

weight of evidence) ●  Truthful and not misleading



Source: Trumbo, FDA, CFSAN

► Health Claims ●  Relationship between a food or food component and a

diseases or a health related condition ●  Premarket review of health claims ●  For labeling of conventional foods and dietary supplements ●  Authorized HC must meet the scientific agreement standard

(SSA) ●  Qualified HC falls short of the SSA standard, but there is

some credible evidence to support the claim ●  Premarket regulatory and scientific review:

o  540 days for authorized HC o  270 days for QHC



Source: Trumbo, FDA, CFSAN

Claims categories Non-‐disease related Disease -‐related

EU Ar>cle 13.1/13.5 Ar>cle 14

US Structure/Func>on Authorized Qualified

Health Claims: EU vs. US



30

EU US

Classifica>on Art 13.1/13.5 S/F

Level of scien>fic evidence required Highest possible standard

Competent & reliable scien>fic evidence

Approval required Yes No*

Posi>ve list of claims Yes No

congruency between claim wording and scien>fic evidence

Some flexibility No

Claim required to be biologically relevant Yes No

Disclaimer required No Yes

Prescribed claim wording Some flexibility No

Applica>on of nutri>onal profiling** Yes No

► Non-disease related

Source: Cantox *in-house scientific substantiation is required **related to daily amounts of fats, sugar and sodium



EU US

Classifica>on Art 14 Authorized (A)/ Qualified (Q)

Level of scien>fic evidence required Highest possible standard

SSA (A)/ <SSA (Q)

Approval required Yes Yes

Disease risk factor must be inden>fied and modified

Yes No

HC wording is prescribed Yes Yes

Applica>on of nutri>onal profiling Yes Yes

Regula>on required Yes Yes (A)/No (Q)

► Disease related

Source: Cantox

► Commonalities between EU and US regulations ●  Claim wording:

o  must be truthful and not misleading ●  Scientific substantiation:

o  Must be based on the totality of scientific evidence o  Pertinent data must be from human studies o  Causality must be established o  Relevance of the scientific data must be established

●  Regulatory oversight: o  Transparency in scientific expectations, evaluation process (if

applicable),and outcome (guidance documents, publication of opinions)

► Elements unique to the EU: ●  Claims related to children’s health and development are considered

separately ●  Potential for claim exclusivity under art. 13.5 (exclusive to product or

product composition)



Source: Cantox

Process of bridging functional foods on the market


Source: IFT

►  KiOnutrime-CG ® is ●  a vegetal high-purity biopolymer comprising two types of

polysaccharides chains: o  chitin: beta(1,4)-poly-N-acetyl-D-glucosamine o  beta(1,3)-D-glucan

●  extracted from the cell walls of the A. niger mycelium ●  a dietary fiber according to definition EC No. 2008/2004

Case study: chitin-glucan as novel ingredient

34 CONFIDENTIAL - Copyright © November 2011 KitoZyme – All rights reserved

►  Animal model ●  18 hamsters ●  12 weeks ●  Atherogenic diet (enriched in saturated fatty acids and cholesterol) ●  Dose : 21.4mg/kg bw/day and 42.8mg/kg bw/day

►  Parameters ●  Blood lipid homeostasis and plaque formation ●  Reactive oxygen species ●  GPx and SOD activity

►  Study center ●  U3762 Aliments et Santé - University of Montpellier 2, France

►  Results ●  Increased antioxidant activity (cardiac production of superoxide anion

and liver MDA, liver superoxide dismutase activity) ●  Reduced triglycerides ●  Reduced aortic fatty streak accumulation ●  Beneficial effects with respect to the development of atherosclerosis

►  . Berecochea-Lopez et al. J. Agr. Food Chem. 2009, 57, 1093-1098

Chitin-glucan beneficial effects- Arterial health


►  CG reduces the accumulation of fatty streak accumulation

►  Light microscopy image analysis of aortic arch sections taken

from hamsters on an atherogenic diet reveals that the aortic fatty streak area is 96% smaller in the group of animals that consumed KiOnutrime-CG ® (Panel B) compared to the control group (Panel A).

► . Berecochea-Lopez et al. J. Agr. Food Chem. 2009, 57, 1093-1098

Chitin-glucan beneficial effects- Arterial health

36

. Control A KiOnutrime-CG® B.

CONFIDENTIAL - Copyright © November 2011 KitoZyme – All rights reserved

►  Protection of cells and tissues from oxidative stress ●  of SOD and GPx (hepatic anti-oxydant enzymes) ●  $ reactive oxigen species ●  $ TBARS values (measure of lipid peroxidation) ●  $ plasma TG

Chitin-glucan beneficial effects- Stimulation of AOX system


Chitin-glucan beneficial effects- Fiber benefits


►  Health effect on obese mice : Nutritional model of obesity ●  24 mice (8 per group) ●  4 weeks dietary intervention ●  Groups:

o  CT= Control Group : mice fed with a balanced AO4 control diet o  HF= Enriched-diet control group : mice fed with a High-Fat diet o  HF+X= Treatment group : mice fed daily with a high-Fat (HF) diet

supplemented with 10% KiOnutrime-CG® ►  Study center:

●  Pharmacokinetics, Nutrition & Toxicology Unit, UCL (BE) - Prof. N. Delzenne

●  Laboratory of Microbial Ecology & Technology, Ghent University (BE) - Prof. W Verstraete

►  Parameters analyzed: ●  Gut microbiota ●  Glucose and lipid metabolism ●  Test for oral glucose tolerance after 3 weeks (OGTT)

►  Results

●  Restores the composition and activity of gut bacteria that is altered by a high fat diet



►  Chitin-glucan decreases body weight gain and fat mass development

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 20 22 24 26 28 30 32 34 36

CT HF HF-CG

Body weight evolution

jour

g

CT HF HF-CG 0.0

2.5

5.0

7.5

10.0 * Body weight gain

§ *

g

CT HF HF-CG 0

500

1000

1500

2000 Caloric intake

kcal

Subcutaneous adipous tissue

CT HF HF-CG 0

1

2

3

4 *

* § %

A. Neyrinck et al. 2011

Effect on glycemia and glucose tolerance


►  After 3 weeks, HF diet induced glucose homeostasis disorders: fasting hyperglycemia, fasting hyperinsulinemia, higher glucose-induced insulin secretion following OGTT and a higher index of insulino-resistance (HOMA-IR)

►  Chitin-glucan improves glycemia and glucose tolerance

Fasting glycemia

CT HF HF-CG 0.0 2.5 5.0 7.5

10.0 * §

mM

Fasting insulinemia

CT HF HF-CG 0

100

200

300 *

*

pM

Glycemia (OGTT)

-30 0 30 60 90 120 5

10 15 20 25

CT HF HF-CG

time

mM

AUC (OGTT)

CT HF HF-CG 0 500

1000 1500 2000 2500 *

* §

mM

.min


Effect on liver and plasma lipid profiles


►  Chitin-glucan changes the liver and plasma lipid profiles and prevents HF-induced hepatic steatosis

HF

HF-CG

Serum lipids-Total cholesterol

CT HF HF-K 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5

* * §

mM

Histological analysis of liver section – Staining with oil red O for lipid detection




►  Chitin-glucan restores the number of Roseburia spp. in the caecum of mice

Bifidobacterium spp.

CT HF HF-CG 7

8

9 *

*

Log 10

[DN

A co

pies

/ g

caec

al c

onte

nt]

Lactobacillus spp.

CT HF HF-CG 7

8

9

10

* * §

Log 10

[DN

A co

pies

/ g

caec

al c

onte

nt]

Bacteroides/Prevotella spp.

CT HF HF-CG 10

11

12

* *

Log 10

[DN

A co

pies

/ g

caec

al c

onte

nt]

Roseburia spp.

CT HF HF-CG 6 7 8 9

10 §

*

Log 10

[DN

A co

pies

/ g

caec

al c

onte

nt]

►  The consumption of chitin-glucan has potential benefitial effects with respect to the development of obesity induced by a high fat diet and with respect to the development of associated metabolic disorders : ●  diabete ●  hepatic steatose ●  hypercholesterolemia

► . A. Neyrinck et al. Dietary modulation of clostridial cluster XIVa gut bacteria (Roseburia spp.) by chitin-glucan fiber improves host metabolic alterations induced by high fat-diet in mice. Journal of Nutritional Biochem. 2011

Conclusions


►  Pilot clinical study: ●  30 males with an average BMI of 24 ±2.5 kg/m2 and a normal cholesterol ●  4 weeks on normal diet ●  Dose: 4.5g / day (n=20; placebo n=10)

►  Study center: ●  University Hospital of Liège (BE), Diabetology, Nutrition and Metabolic Diseases

Department - Prof. Nicolas PAQUOT

►  Outcome measures: ●  Cardiovascular and anti-oxidant markers including oxidized LDL-Chol

► Results ●  Decrease in oxidized-LDL ●  Prevention from atherosclerosis

risk ●  Safety and well -tolerated

►  . Deschamps et al. Managing oxidative stress with a vegetal ingredient, chitin-glucan. AgroFOOD 2009

CONFIDENTIAL - Copyright © November 2011 KitoZyme – All rights reserved

Pilot clinical study

44

►  Study protocol ●  135 patients with an average BMI of 18.5 - 34.9 kg/m2 LDL-chol: ≥130 – 189.9 mg/dl ●  6 weeks intervention ●  4 groups:

o  4.5 g/day of chitin glucan o  1.5 g/day of chitin glucan o  1.5 g/day of chitin glucan in a combo o  Placebo

►  Multi-center study (US/CA) ►  Parameters analyzed:

●  Primary study endpoint is the between-group difference oxLDL ●  Secondary study endpoints are between-group differences LDL-chol, total chol, HDL-

chol, triglycerides, glucose, insulin, F2-isoprostanes (urine). ●  Safety endpoints

► Data analysis and manuscript submitted for publication

A Randomized, Double-Blind, Placebo-Controlled Study of the Effects of Chitin-Glucan on Ox-LDL

45

► Stability ► Functional and sensory

quality ► Successful

development in bars, dairy, bakery, smoothies, soft chews, chewable tablets etc…

Chitin-glucan in functional food


►  EUROPE o  Feb. 2011: NOVEL FOOD Authorization for KiOnutrime-CG (ARTINIA) in Europe

under Regulation (EC) N° 258/97 (Full application) −  Novel Food according to Regulation (EC) 258/97 −  Jan. 2008: File submission to Belgian Public Health authorities −  Sept. 2009: Scientific evaluation by EFSA (Panel on Dietetic Products, Nutrition and

Allergies) −  July 2010: Positive opinion from EFSA

o  « Chitin-Glucan from Aspergillus niger was safe under the proposed conditions of use and the proposed levels of intake

►  US o  Dec. 2010: GRAS Self–Affirmation for KiOnutrime-CG (ARTINIA) as a Direct and

Secondary Direct Food Ingredient in a Variety of Foods and Beverage ►  CANADA

o  May 2011: Natural Health Product (NHP) Master File for KiOnutrime-CG (ARTINIA)

►  ASIA o  Aug. 2011: Approval of KiOnutrime-CG (ARTINIA) as a food ingredient by the

Tawain-FDA ►  RUSSIA: registration ongoing

Regulatory process


Partnership with NOVUS (Stratum Nutrition)


Jan. 2010: Strategic partnership agreement between kitoZyme and Stratum Nutrition for the global commercialization of chitin-glucan in human nutrition

−  finalisation of the R&D plan −  clinical study −  product launching

www.stratumnutrition.com

ARTINIA™ is a novel fiber for arterial health.

Thank you!

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A la rencontre des aliments fonctionnels : du ... · A la rencontre des aliments fonctionnels : du développement à la ... from adding new substances to an individual’s diet. Functional