4 december 2020

CONFIDENTIAL

Perspective on Dairy Proteinsin Medical NutritionFocus on high protein ONS drink

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for better food & healthNIZO

• Independent, private contract research company for food and health

o Protein Transitiono Smarter Processingo Food Safety & Chain Controlo Health Benefits

Application & Processing Centre

Research Center

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Topics

• Introduction to medical nutritiono Market potentialo High protein ONS drink

• Importance of dairy protein in high protein ONS drinko Nutritional aspecto Technical challenges

• Concluding remarks

Application & Processing Centre

Research Center

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Medical nutrition: Needs & market growth

• Nutritional products are used under medical supervision to manage disease- or condition-related dietary needs

• World’s population over 65 years will double from 8% to 16% in 20501

1. Medical Nutrition Market Research Report – Global Forecast till 2023 (MRFR, 2019)2. Clinical Nutrition Market Size by Product, Parenteral Nutrition, Enteral Nutrition… (Global Market Insights, 2019)Nutrifacts: The Who, What and Why of Medical Nutrition (2018)

•Frail elderly patients•Dysphagia•Pre- and post- surgery•Diabetes

•Chronic kidney disease•Digestive tract disorders•Cancer patients •Hospitalized patients

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DRM: disease related malnutrition

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Medical nutrition: Oral nutritional supplements (ONS)

Medical Nutrition International Industry (2018)

- Nutrients- Taste- Stability

33 milpeople are at

risk of malnutrition

in EU

1 in 4 hospital

patients are malnourished

This costs EU countries

€170 bil.

Malnutritionincreases

hospital stay

up to 75%

Reduce thecost of

hospitalcare by 12%

Improvepatients’ quality of

life

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Medical nutrition: Important factors for high protein ONS drink

Source: Nieuwenhuizen, et al. Older adults and patients in need of nutritional support: Review of current treatment options and factors influencing nutritional intake. Clinical Nutrition, 2010; 29 (2): 160-169

Proteinquality

Protein quality to match the intended needs of patients

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Nutritional aspect of protein

Berrazaga, I, et al. The role of the anabolic properties of plant- versus animal-based protein sources in supporting muscle mass maintenance: a critical review. Nutrients. 2019; 11 (8): 1825Chalupa-Krebzdak, et al. Nutrient density and nutritional value of milk and plant-based milk alternatives. International Dairy Journal. 2018; 87: 84-92

Dairy vs plant protein1

- Higher essential amino acid content- Better digestibility- Contains higher mineral content with

relatively higher absorbability

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Digestibility of various protein (NIZO example)

Potato

Soybean

Pea

Dairy

In vitro digestibility increased with: low MW potato < casein < high MW potato < pea < soy << whey proteinA similar trend was observed for the in vivo amino acid digestion profiles: TAA, EAA, BCAA and Leucine

T. He, R.E.J. Spelbrink, B.J. Witteman, and M.L.F. Giuseppin (2013) Int J Food Sci Nutr; 64(7): 787–793.

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Medical nutrition: Important factors for high protein ONS drink

Nieuwenhuizen, et al. Older adults and patients in need of nutritional support: Review of current treatment options and factors influencing nutritional intake. Clinical Nutrition, 2010; 29 (2): 160-169 Brown, A. et al. 2013. The liking and preferences of people withthoracic cancer for oral nutritional supplement drinks. E-SPEN Journal 8 (2): e55-e58. Rahemtulla, Z. et al. 2005. The palatibility of milk-based and non-milk-based nutritional supplements in gastrointestinal cancer and the effect of chemotherapy. ClinicalNutrition 24 (6): 1029-1037 Darmon, P. et al. 2008. Oral nutritional supplements and taste preferences: 545 days of clinical testing in malnourished in-patients. Clinical Nutrition 27 (4): 660-665.

Build-up of taste and mouthfeel are not preferred1

Liking to dairy-based ONS >> juice / yoghurt type1,2,3,4

Proteinquality

Palati-bility

Protein quality to match the intended needs of patients1

Low volume

(compact nutrient)

Liquid & low

viscosity

For ease of consumption1

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High protein ONS drink: Challenge in formulation

Different countries/regions have their ownguidances on the nutrient required in medical food

o FDA o FSMP o NMPA

Some ingredients may bring additional(necessary) nutrient, e.g. milk protein

Mixture of various ingredient to fulfillspecific nutrient is common

Per 100 ml:220 kcal9% protein6% fat32% carbs

Per 100 ml240 kcal14.4% protein9.4% fat24.4% carbs29 g

6 g

32 g

67 g 80 g

Increasing possibility of ingredientsinteraction

46 g

9.4 g24.4 g

High protein, “pure” ingredient is needed

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High protein ONS drink: Challenge in processing

emulsificationdissolving sterilizationstandardization filling

Ingredientinteraction during

processing

pH Heating (T/t)

~30 ingredients

shelf life

Influence proteinbehavior, and thus

product characteristic

Long list of ingredients in medical nutritions to complyto regulation and to contributeto a stable, good product typically contain sources of:

- Proteins- Carbohydrates- Fats- Fibers - Whole range of minerals- Whole range of vitamins- Flavors- Colorant- pH regulator- Stabilizer

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• Low volume + low viscosity are key for high protein drink• Techno-functionality of dairy proteins are better than plant

protein (here represented by PPI) to achieve this goal• At 10% protein, high protein ONS drink made from PPI turned

to gel after heating→ not suitable for application in drink

0

2

4

6

8

10

0,01 1,00 100,00 10000,00

Vo

lum

e Fr

acti

on

(%

)

Particle Size (µm)

Particle size distribution of 5% proteindrink

MCI MPI NaCas WPI PPI

MCI: micellar casein isolateMPI: milk protein isolateNaCas: sodium caseinateWPI: whey protein isolatePPI: pea protein isolate

150 kcal5 % protein21 % carbs5 % fat

Retorted ONS drink prototypes

MCI MPI NaCas WPI PPI

At 10% protein

Source: internal NIZO data

0

20

40

60

80

100

MCI MPI NaCas WPI PPI

Vis

cosi

ty (

mPa

.s)

Viscosity of 5% protein drink

High protein ONS drink: Why dairy proteins are still preferred overplant proteins (NIZO example)

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High protein ONS drink: Influence of pH (NIZO example)

• pH influence on how proteins behave: interaction under theapplied heat treatment

• The effect is more apparent in product with higher proteincontent → increasing importance to choose the right pH and heating condition

0

20

40

60

80

100

pH 6.6 pH 7.2 pH 6.6 pH 7.2 pH 6.6 pH 7.2 pH 6.6 pH 7.2

MCI NaCas WPI PPI

Vis

cois

ty (

mPa

.s)

Viscosity of 5% protein drink

0

10

20

30

40

50

pH 6.6 pH 7.2

MCI

Vis

cosi

ty (

mPa

.s)

Viscosity of 12.5% protein drink

150 kcal5 % protein21 % carbs5 % fat

Retorted ONS drink prototypes

Source: internal NIZO data

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High protein ONS drink: Why casein is preferred over whey

Casein• No denaturation• Relatively heat stable

-

--

--

---

----

- - -

K-casein provides heat stability: electrostatic repulsion and steric hindrance

-

--

--

---

----

- - -

Only start to aggregates at really high concentration, due to:• Heat-induced hydrolysis of k-casein• High calcium concentration which screens electrostatic repulsion

& trigger calcium bridges

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High protein ONS drink: Why casein is preferred over whey

Whey protein• Denature upon heating• Cause protein aggregation

2. -Lg + -Lg

Aggregates

Gel

at high

H-S

S-H1. -casein + -Lg

S-S link

Native -lg Unfolded -lg* Aggregated -lgS-H

S-HT>70°C

Gel

at high

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High protein ONS drink: Why casein is preferred over whey (NIZO example)

0

5

10

15

20

25

30

35

5% 10% 12,5%

Vis

cosi

ty (

mPa

.s)

Protein concentration

Viscosity of ONS prototypes

MCI

MPI

WPI

• At ≥10% protein, WPI-based ONS drink showed visible aggregate andthick product

• At ≥12.5%, MPI-based ONS drink showed visible aggregates and thickproduct

Ge

l fo

rme

d

Ge

l fo

rme

d

Ge

l fo

rme

d

At neutral pH, casein is much more preferred over whey protein as the

protein source for high protein drinks

Source: internal NIZO data

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High protein ONS drink: Not all caseins behave the same (NIZO example)

Micellar casein

Voluminosity 4.1 ml/g at 20 oC1

1. Nobel, S. et al. 2012. Apparent voluminosity of casein micelles determined by rheometry. Journal of Colloid and Interface Science 386 (1): 174 – 1802. Ruis, H. 2007. Structure-rheology relations in sodium caseinate containing systems. PhD Thesis Wageningen University.

Sodium caseinate

Voluminosity 6.1 ml/g at 20 oC2

Einstein’s and Eiler’s equation showed direct correlation of voluminosity to viscosity.

1

10

100

1000

5% 10%

Log

Vis

cosi

ty (

mPa

.s)

Protein concentration

Viscosity of ONS prototypes

MCI

NaCas

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Requirement on nutrient composition of medical nutritionChallenge in using micellar casein in high protein ONS drink

Example of MCI composition• Protein: 76.5 g/100 g • Calcium: 2200 mg/100 g powder• Phosphorus: 1500 mg/100 g powder

Micellar casein

0

100

200

300

400

500

600

700

0 5 10 15 20 25co

nce

ntr

atio

n (

mg

/10

0 g

)Protein concentration from MCI (g/100 g)

*For a drink with 240 kcal/100 ml

Source: Comission Directive 1999/21/EC. 1999. on dietary foods for special medical purposes. Official Journal of the European Communities.

Ca

P

FSMP guideline for max P

FSMP guideline for max Ca

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Sensitivity to changes in environmentChallenge in using micellar casein in high protein drink

Source: Broyard, C. and Gaucheron, F. 2015. Modifications of structures and functions of caseins: a scientific and technological challenge. Dairy Science & Technology 95: 831-862.

21Source: Le Ray et al. 1998. Heat stability of reconstituted casein micelle dispersions: changes induced by salt addition. Lait 78:375-390

Challenge in using micellar casein in high protein ONS drink

Ca2+

Ca2+Ca2+

Ca2+

Ca2+Ca2+

Intense heatingdissociates k-casein

The exposed Ca-sensitivecalcium starts to aggregate

when heated

High protein increases Ca2+ concentration & reducesproximity between micelles

Ca2+ screens negative charges and heating triggers aggregation

CaCa Ca

Ca

Ca

Ca

Ca

CaCa

Ca

Ca

Understanding casein micelle’s sensitivity to heat and calcium

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Citrate is often used in high protein ons drink to improve heat stabilityUnderstanding the role of chelators

Citrate will chelate free calcium, preventing the calcium

to interact with the proteins

Citrate3-

Citrate3- Citrate3-

Citrate3-

Ca2+

Ca2+Ca2+

Ca2+

Ca2+Ca2+

CaCitrate

CaCitrateCaCitrate

CaCitrate

Source: internal NIZO data

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… however the addition of citrate can trigger other challenges to appear

Swollenmicelle

CaCitrate

Increased viscosity

Saturated CaCitrate formscrystal precipitate in product

Dissociatedmicelle

24Broyard, C. and Gaucheron, F. 2015. Modifications of structures and functions of caseins: a scientific and technological challenge. Dairy Science & Technology 95: 831-862.

Challenge in using micellar casein in high protein ONS drink: sensitivity to changes in environment

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Concluding remarks

Respectable market growth for medical nutrition due to growing population and increasing lifeexpectancy

Extensive knowledge on dairy protein characteristic and interaction with other ingredients is importantfor the success in formulation of high protein ONS drink

Dairy protein is essential for high protein drink: preferred nutrition (good amino acid composition),technological property (high heat stability), and taste compared to plant protein

At the moment, plant protein could not match the use of dairy protein in high protein ONS drink.However, innovations are ongoing, and some products already contain mixture of both.

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