does homogenization affect the human health...

Does homogenization

affect the human

health properties of

cow’s milk?

Marie-Caroline Michalski*,1

and Caroline Januel&

UMR INRA 1253, Science et Technologie du Lait et

de l’Œuf, Agrocampus Rennes, 65 rue de

Saint-Brieuc, 35042 Rennes Cedex, France

During the processing of marketed milk, homogenization

reduces fat droplet size and alters interface composition by

adsorption of casein micelles mainly, and whey proteins.

The structural consequences depend on the sequence of the

homogenization and heat treatments. Regarding human

health, homogenized milk seems more digestible than

untreated milk. Homogenization favors milk allergy and

intolerance in animals but no difference appears between

homogenized and untreated milk in allergic children and

lactose-intolerant or milk-hypersensitive adults. Controver-

sies appear regarding the atherogenic or beneficial bioactiv-

ity of some casein peptides and milk fat globule membrane

proteins, which might be enhanced by homogenization. In

children prone to type I diabetes, early cow’s milk

consumption would be a risk but no link was observed in

the general population and the effect of homogenization has

not been studied. In the current context of obesity and

allergy outbreaks, the impact of homogenization and other

technological processes on the health properties of milk

remains to be clarified.

0924-2244/$ - see front matter q 2006 Elsevier Ltd. All rights reserved.doi:10.1016/j.tifs.2006.02.004

* Corresponding author.1 Now present at: INRA UMR 1235/INSERM U 449, MecanismesMoleculaires du Diabete, Faculte de Medecine R. Laennec,Universite Claude Bernard Lyon I, 8 rue Guillaume Paradin,69372 Lyon cedex 08, France. Tel.: C33 47 877 1046; fax: C3347 877 8762; e-mail: [email protected]

IntroductionMilk is a complex biological fluid composed of water,

fat, proteins (mainly casein micelles and whey proteins),

carbohydrates (mainly lactose) and quantitatively minor

though bioactive components: minerals, vitamins and

enzymes (Jensen, 1995). Cow’s milk is a nutritive food

regarding human health and a functional food on a

technological viewpoint. Fat is present in milk in the form

of fat globules in suspension in the aqueous phase. Milk fat

is composed mainly of triacylglycerols and some diglycer-

ols, complex lipids and unsaponifiable lipophilic com-

pounds (Table 1). The milk fat globules are surrounded by a

native biological membrane (Fig. 1) composed mainly of

phospholipids, proteins and enzymes, cholesterol, glyco-

proteins, vitamins: the milk fat globule membrane (MFGM;

Mather, 2000). Saturated fatty acids represent 60–70%

(w/w) of total milk fatty acids and unsaturated fatty acids

30–35% (mainly mono-unsaturated). Moreover, each fatty

acid has a preferential position on the triglycerol backbone

so that thousands different triacylglycerols are found in milk

fat (Jensen, 2002). The role of milk fat in contributing to

health and disease is quite controversial (Berner, 1993a).

While saturated fatty acid and cholesterol contents are

suspected to take part to the risk of coronary heart disease,

some milk lipids such as conjugated linoleic acids (CLA),

sphingomyelin and butyric acid would present anti-

carcinogenic properties (Parodi, 1997).

Regarding proteins, four casein classes coexist (as1, as2,b, k) with similar composition, rich in glutamic acid, leucin,

serine, lysine and prolin. They are all phosphoproteins of

150–200 amino acids, differing in the number of phospho-

seryl groups, the presence of cystein, carbohydrates and

content in some amino acids. Caseins, that do not present

secondary structure, are organized as so-called micelles via

hydrogen bonds, hydrophobic, electrostatic and disulfide

bonds, and different salts are involved (calcium, phos-

phorus, magnesium, citrate). The k-casein is located at the

surface of the micelle, which is held together by calcium

phosphate bonds. The soluble proteins (whey proteins)

represent only 15–22% of milk proteins but form a complex

group consisting of albumins, immunoglobulins and

proteose–peptones. They are globular proteins (presenting

secondary—a-helix and b-pleated sheet—to quaternary

structure) whose high lysine, tryptophan and cysteine

content provide a great nutritional value. They contain

less proline than the caseins and are compact molecules.

Trends in Food Science & Technology 17 (2006) 423–437

Review

Table 1. Gross composition of milk lipids (adapted from Walstra, Geurts, Noomen, Jellama, & van Boekel, 1999; Jensen, 2002)

Content in totalfat (%, w/w)

Fraction inglobule core (%)

Fraction inMFGMa (%)

Fraction in skimphase (%)

Neutral glyceridesTriacylglycerol 95.8–98.3 100Diacylglycerol 0.28–2.25 z90 z10 ?Mono-acylglycerol 0.03–0.38 Traces Traces Traces

Free fatty acids 0.10–0.44 60 z10 30

Phospholipids (incl. sphingomyelin) 0.20–1.11 – 65 35Cerebrosides 0.1 – 70 30Gangliosides 0.01 – z70 z30

Sterols 80 10 10Cholesterol 0.30–0.46Cholesteryl ester %0.02

CarotenoidsCvitamin A 0.002 z95 z5 Traces

a Native milk fat globule membrane.

M.-C. Michalski, C. Januel / Trends in Food Science & Technology 17 (2006) 423–437424

They are more heat sensitive than caseins (the latter are

stable until 100 8C): heat treatments cause their denatura-

tion, aggregation and insolubilization. The denaturation and

insolubilization rates depend on the protein class and

physico-chemical conditions. b-Lactoglobulin (b-Lg) is

the most abundant whey protein (51%) and can bind and

transport small hydrophobic molecules such as retinol

(vitamin A precursor). a-Lactalbumin (a-La) represents

22% of whey proteins and is involved in lactose synthesis

(Jensen, 1995; Whitney, 1988). Individual milk proteins

have a wide range of beneficial health and functional effects

via bioactive peptides, such as anti-carcinogenic effects,

enhancement of certain physiological functions (Meisel,

2005; Silva &Maltaca, 2005), improved iron bioavailability

(Bouhallab & Bougle, 2004) or prevention of dental caries

(Aimutis, 2004). On the other hand, milk proteins are also

important food allergens (Host, 2002) and are suspected to

be involved in some diabetes cases (Schrezenmeir & Jagla,

2000). In this respect, the issue of milk as a healthy or

deleterious foodstuff remains controversial in many aspects.

Marketed milk is manufactured from raw milk obtained

from sane cows, subjected to various processing steps in

order to collect and preserve milk along the supply chain:

machine milking, cooling, cold storage, homogenization,

heat treatment, packaging and storage. Each one of

these processing steps induces changes in the intrinsic

quality of milk (Table 2). This article will focus on

homogenization, which results in the most profound

changes in the physical structure of milk and might result

in altered health properties. Homogenization is defined as

the process of subdividing the relatively large polydisperse

oil globules of a coarse oil-in-water emulsion into a large

number of smaller globules of narrow size range. Milk is

pressurized in order to destroy milk fat globules into fine

lipid droplets, thereby preventing the cream separation

(Mulder & Walstra, 1974). Though, homogenization does

not kill microorganisms, so that intensive heat treatments

(pasteurization or UHT, ultra high temperature process) are

necessary in order to preserve product microbiological

quality (Hui, 1993, Chapter 5). Pasteurization consists in

heating milk at 72 8C for 15 s then cooling it immediately. It

is sometimes necessary to heat milk up to 85 8C during 20 s.

The UHT process allows shortening of the heating step:

140–150 8C during a few seconds. Extended shelf-life of

chilled product can also be achieved by bacteria removal

using microfiltration (Saboya & Maubois, 2000). Heat

treatments are used to preserve milk easier, but they

enhance the impact of homogenization on the organization

of milk, and possibly on its quality and health properties.

Firstly, the different homogenization processes will be

summarized. The consequences of homogenization and heat

treatment sequences on milk structure will be described.

Finally, we will evaluate the possible effects of homogen-

ization on the health properties of milk through literature

evidence or suggestions and highlight research area that

should be further explored.

Principles of homogenizationThroughout the Western world, commercial milk is

homogenized and heat-treated. Homogenization has been

set-up by August Gaulin at the early 20th century; it consists

in forcing pressurized milk (8–20 MPa) between a valve

needle and seat (Gaulin-type homogenizer), resulting in a

dramatical reduction in fat globule size due to shear stress,

inertial forces and cavitation. A second stage processed at

lower pressure dissociates aggregates formed at the first

stage (Pouliot, Paquin, Robin, & Giasson, 1991). Homo-

genization is usually operated at 60 8C, though pressure and

temperature conditions vary according to apparatus and

valve type (Paquin, 1999; Wilbey, 2002). Homogenization

efficiency increases with temperature from 42 to 72 8C and

stabilizes around 72–77 8C (Hui, 1993, Chpater 5).

According to Stoke’s law, the smaller milk fat globule

size dramatically decreases the cream separation rate that is

due to the density difference between milk fat and

the aqueous phase. To some extent, it also prevents

coalescence; the milk emulsion is thus more stable and

shelf-life increases.

Fig. 1. Organization of the native milk fat globule membrane (MFGM) compared with the interfacial organization of an homogenized fatdroplet, and proposed general organization of lipid particles in homogenized milk: ( ) native milk fat globule, ( ) casein micelle, ( ) fragmentof casein micelle, ( ) whey protein, ( ) fragments of MFGM (structure and location of the latter in the skim phase remain to be characterized).

Adapted from Michalski et al. (2001, 2002b).

M.-C. Michalski, C. Januel / Trends in Food Science & Technology 17 (2006) 423–437 425

Microfluidization is another homogenization technique

by which the fluid is forced under high pressure

in the reaction chamber and is divided into two jets

colliding at 1808 at high speed. At a given pressure, a

microfluidizer produces significantly narrower fat globule

size distributions compared with a regular homogenizer and

the mean diameter is also smaller (Hardham, Imison, &

French, 2000; Pouliot et al., 1991). This improves emulsion

long-term stability, therefore, microfluidization is advan-

tageous for long shelf-life such as UHT products (Hardham

et al., 2000; Pouliot et al., 1991).

High pressure homogenization (HPH) is based on the

regular homogenization technique but is operated at higher

pressure (O50–100 MPa). It is used to disperse non-miscible

Table 2. Major milk changes induced by the processing chain (adapted from Korhonen and Korpela, 1994; Morr & Richter, 1988)

Unit process Related reaction Consequences

Machine milking Lipid oxidation Peroxides, oxidized tasteLipolysis Free fatty acids, rancid taste

Cooling, agitation, coldstorage

Dissolution of casein micelles Aggregation of casein and calcium phosphateFat crystallization Alteration of the milk fat globule membraneLipolysis Free fatty acids, rancid taste, oxidative off-flavorProteolysis Peptides, free amino acids

Homogenization Fat globule disruption Smaller fat globules with a new interfaceDispersion of casein micelles Formation of fat-protein complexesActivation of some enzymes Oxidized taste, rancid taste

Heat treatment Destruction of microorganisms Increased microbiological quality and shelf-lifeWhey protein denaturation Formation of casein–whey protein complexesLactone formation Enhanced flavor and tasteEnzyme inactivation Increased quality and shelf-life

Pasteurization Destruction of water-soluble vitamins !10% Vitamin B; !25% Vitamin CUHT Destruction of water-soluble vitamins !20% Vitamin B; !30% Vitamin C

Maillard reaction Lactose–protein complexes, partial loss of lysineLactose isomerization Formation of lactulose

Storage of packed: Reactivation of enzymes Organoleptic defects (proteolysis, lipolysis)Pasteurized milk Growth of psychrotrophic bacteria Bitter taste due to proteolysis

Destruction of water-soluble vitamins !30% of Vitamins B and CUHT milk Age gelation Formation of protein-mineral complexes

Destruction of water-soluble vitamins !50% Vitamin B; O90% Vitamin C


phases, stabilize emulsions and/or prepare products with

appropriate rheological properties (Floury, Desrumaux, &

Lardieres, 2000). The fat droplet size decreases when the

HPH pressure increases (50–200 MPa) and at given tempera-

ture and pressure, the HPH fat droplets are significantly

smaller than regularly homogenized ones (Hayes & Kelly,

2003a). However, HPH (40–60 MPa) results in off-flavors in

milk, probably due to oxidation. Homogenization at 20 MPa

does not cause such off-flavor (Humbert, Driou, Guerin, &

Alais, 1980). One advantage of HPH is to reduce bacterial

microflora (Hayes, Fox, & Kelly, 2005; Thiebaud, Dumay,

Picart, Guiraud, & Cheftel, 2003). The size of casein micelles

decreases at pressures greater than 200 MPa. HPH inactivates

plasmin (Hayes & Kelly, 2003b) and reduces alcaline

phosphatase and lactoperoxidase activities (Hayes et al.,

2005). The major drawback of high-pressure treatment is the

high cost of the equipment required. HPH is suggested to be

possible novel milk processing technique-combining advan-

tages of homogenization and pasteurization in a single

process (Hayes et al., 2005).

Consequences of homogenization on milkcomponents

The composition of the MFGM is altered by heat

treatments and homogenization (Mulder & Walstra, 1974).

The effects of these treatments on milk organization are

often controversial. Fig. 1 schemes the organization of the

native MFGM and the solely homogenized fat droplet.

Moreover, the consequences of homogenization on the

organization of milk depend on the sequence and type of

homogenization and heat treatments, as also pointed out

using HPH with skim milk (Sandra & Dalgleish, 2005).

Effect of homogenization and heat treatments onproteins, phospholipids and vitamins

The main effect of homogenization on soluble milk

components is the disruption of casein micelles while

adsorbing at the interface, in micellar form or as fragments.

Moreover, at least one of the agglutination factors is

inactivated (Walstra, 1980) and some MFGM components

are displaced to the skim milk phase during homogenization

(Keenan, Moon, & Dylewski, 1983). Bovine xanthine

oxidase (BXO) and butyrophilin are covalently bound to

fatty acids, contributing to the lipophilicity of these proteins

and the preservation of their affinity with the interface

despite the physical stress caused by homogenization. The

phospholipid content of the new membrane appears slightly

lower than that of the MFGM (McPherson, Dash, &

Kitchen, 1984a). The material loss appears not to be

selective. HPH decreases the casein micelle size in skim

milk, e.g. from w209 nm at 41 MPa down to w190 nm at

186 MPa (Sandra & Dalgleish, 2005); though, it is not

known whether micelle size decreases in HPH homogenized

whole milk.

During milk heating, chemical and enzymatic reaction

rates increase, as well as bacteria disruption (Renner, 1988).

Whey proteins are more heat sensitive than caseins. The

extent of denaturation depends on heat treatment type

(neglectable during pasteurization; 20% of whey proteins

denatured at 80 8C for 1 min vs 60% with UHT process) and

protein type, b-Lg being more heat sensitive than a-La(Kinsella & Whitehead, 1989). Moreover, in skim milk,

heat-induced binding of denatured proteins to casein

micelles provokes pH-dependent increased micelle size

and inter-micelle interactions (Anema & Li, 2003; Jeurnink


& De Kruif, 1993). Caseins are much more heat resistant,

particularly b-casein. Several studies have shown that milk

heating induces complex formation between k-casein and a-La via a b-Lg–a-La complex (Elfagm & Wheelock, 1978).

Other studies have shown, using in vitro models (Haque,

Kristjanssan, & Kinsella, 1987; Jang & Swaisgood, 1990)

and skimmed milk (Dalgleish, 1990), that heat-induced

b-Lg–k-casein interactions are mainly due to hydrophobic

interactions and disulfide bond formation. During the

formation of such k-casein–whey protein complexes, both

soluble and micelle-linked aggregates are formed (Anema

& Li, 2003; Guyomarc’h, Law, & Dalgleish, 2003;

Vasbinder, Alting, & de Kruif, 2003). Primary b-Lg–a-Laaggregates seem to be implied in micellar aggreates as well

as k and as2-caseins. Heat-dissociated micellar k-casein is

implied in the formation of soluble aggregates and a

significant part of k-casein is not complexed after heat

treatment.

Heat also favors glycation (also called non-enzymatic

glycosylation or Maillard reaction): the initial reaction

consists in nucleophilic condensation of a sugar free-

aldehyde group and a protein amine group (terminal or

often from lysine). Heated milk is sensitive to glycation

due to its lactose content (Morgan, Leonil, Molle, &

Bouhallab, 1999). Among vitamins, only vitamins B1, B6,

B12 and C and folic acid are heat sensitive, but water-

soluble vitamins are sensitive to storage time (Renner,

1988; Table 2).

Effect of homogenization and heat treatmentson fat droplet size and z-potential

Shear stress and inertial forces induced by pumping are

maximal during homogenization (Corredig & Dalgleish,

1996). This induces fat globule disruption since the former

are greater than the Laplace pressure of the native milk fat

globules. In the following, we will thus refer to fat droplets,

different from the native milk fat globules. The native milk

fat globule size distribution spans from !1 to w20 mm,

with an average volumic size initially around 3–5 mm. Upon

homogenization, the latter is reduced to around 1 mm,

resulting in a 4-to 10-fold increase of the interface between

fat droplets and the aqueous medium (Keenan et al., 1983).

A relationship is given between the volume–surface average

diameter of the fat droplets (d32) and the homogenizing

pressure P: log10 d32ZaKb log10 P, with parameters such

as aZK2 to K1.8 and bZ0.6–0.71 (Michalski, Michel, &

Briard, 2002; Walstra, 1995). Particles between 100 and

400 nm even appear during regular homogenization

(Michalski, Michel, & Geneste, 2002), while the smallest

native milk fat globules (w100–200 nm; Walstra (1969))

should not be affected due to their higher Laplace pressure.

Heat treatment, when not associated with homogenization,

does not induce changes in the milk fat globule size. When

both processes are operated, regardless of order, fat droplets

tend to be smaller than in milk solely homogenized,

resulting in a greater droplet surface area (Lee, 1997;

Sharma & Dalgleish, 1994). In commercial pasteurized or

UHT full-fat milk, the d32 is in the range 0.20–0.25 mm,

calculated from the measured specific surface area (S) of

27–33 m2 gK1 (Lopez, 2005); the corresponding volumic

average diameter (d43) is in the range 0.37–0.49 vs 4.07 mmfor raw whole milk. Fave, Coste, and Armand (2004) report

d43Z0.46–1.02 mm in half-skimmed commercial UHT milk

vs 4.36 mm in whole pasteurized organic milk. In

microfluidized milk, d32 values of 0.30 and 0.24 mm are

reported at 50 and 200 MPa, respectively (Olson, White, &

Richter, 2004).

The electrokinetic potential (z-potential) of a particle is

defined as the potential at the shear layer located farther out

the Stern layer. For native milk fat globules, average znativeis K13.5 mV (Michalski, Michel, Sainmont, & Briard,

2001). The absolute value of z increases with homogenizing

pressure for milk fat droplets, up to a plateau value of

z around K20 mV for strongly homogenized ones

(PO30 MPa). This value corresponds to the z-potential of

casein micelles adsorbed at the droplet interface (Fig. 1).

Indeed, z of homogenized droplets is linked to the surface

fraction F that is not covered by the native MFGM

anymore: zZznative½1C ðKLnð1KFÞ=10:82Þ1=2� (Michalski

et al., 2001). Heating at 80 8C (15 min) results in only small

changes in the micellar z (Anema & Klostermeyer, 1997).

The z-potential of whey protein–k-casein complexes is

reported to be K17 mV (Jean, Renan, Famelart, &

Guyomarc’h, 2006).

According to these structural measurements, homogen-

ized milk is found to be composed of three types of particles

(Michalski et al., 2002b): (i) regular homogenized milk fat

droplets (disrupted globules from the main population,

whose surface fraction covered by caseins can be calculated

from their increase in specific surface area, the rest of

the surface being still covered by MFGM); (ii) small

(!500 nm) lipid–protein complexes having a new

membrane, presumably mainly composed of caseins; and

(iii) tiny native milk fat globules around 100 nm (that were

originally present in milk as a separate population and

should not be affected by homogenization due to their

small size).

Effect of homogenization and heat treatmentson the fat droplet interface

The rupture of fat globules occurring during homogen-

ization creates a new interface that cannot be entirely

covered by the MFGM and can be measured by the

increased S of fat droplets. Therefore, other surface active

components adsorb and form a new membrane (Darling &

Butcher, 1978). Casein micelles are the major protein

fraction adsorbed, even if part of the native MFGM remains

associated to the fat droplets (Jackson & Brunner, 1960). In

a proportion increasing with P (Fox, Holsinger, Caha, &

Pallansch, 1960; Henstra & Schmidt, 1970), casein micelles

would spread onto the fat surface when colliding during

homogenization.


A fourfold increase of total proteins occurs in the

membrane when milk is either solely homogenized or

homogenized and heated (regardless of the sequence of

both treatments) compared to the total membrane proteins in

untreated or solely heated milk (Lee, 1997). After heating at

80–85 8C (10 min), total protein increases in the fat droplet

membrane (Dalgleish & Banks, 1991; Houlihan, Goddard,

Kitchen, & Masters, 1992). Heating increases the ability of

whey proteins to interact with MFGM proteins and/or caseins

adsorbed onto the membrane during homogenization. This

would not always be compensated by the desorption of

MFGM proteins that was highlighted by Houlihan et al.

(1992). If milk is homogenized (50 8C, 17 MPa) then

pasteurized (HTST), caseins represent 99% of adsorbed

proteins, among which b-casein represents 40.8%, as-casein35.7% and k-casein 23.5% (Zahar & Smith, 1996). This does

not reflect untreated milk (Table 3): a preferential adsorption

of k- and b-caseins occurs during homogenization. Signifi-

cant amounts of para-k-casein (N-terminal fragment of

k-casein) were detected in homogenized droplet membranes

(McPherson, Dash, & Kitchen, 1984b). This could be partly

explained by the action of heat stable proteinases on the

b-Lg–k-casein complexes associated with the membrane

(Garcia-Risco, Ramos, & Lopez-Fandino, 2002). However,

the relative amount of para-k-casein compared to b-Lg is

higher than observed in pasteurized milk (McPherson et al.,

1984b). Para-k-casein could also be formed by direct

k-casein hydrolysis at the fat droplet surface during

homogenization. It could preferentially adsorb onto lipid

droplet surface due to its higher hydrophobicity compared

with k-casein. However, several teams have found the b-Lg–k-casein complexes formed during heat treatments in the

membranes of homogenized milk (Houlihan et al., 1992).

Denatured b-Lg is linked to the casein micelles adsorbed on

the fat droplets via k-casein (Dalgleish & Sharma, 1993).

Heat not only causes whey protein binding to adsorbed

micelles, but also reorganizations among casein micelles

themselves (Dalgleish & Sharma, 1993).

Caseins are the major protein fraction adsorbed.

Regarding whey proteins, b-Lg is the main one associated

with the lipid droplets but a small quantity of a-La was alsodetected (Lee & Sherbon, 2002). Using infant formula

pasteurized then homogenized, the pasteurization step

favors b-Lg–k-casein interactions. The caseins and whey

proteins interact with the fat droplet membrane after

homogenization of these formulae (Guo, Hendricks, &

Table 3. Distribution of casein species in untreated milk (Hui,1993, Chapter 5) and at the interface of homogenized andpasteurized milk fat droplets (Zahar & Smith, 1996)

Untreatedmilk (%)

Homogenized and pasteurizedmilk fat droplets (%)

as1-Casein 3735.7

as2-Casein 11b-Casein 34 40.8k-Casein 12 23.5

Kindstedt, 1998). At average homogenization applied to

pasteurized milk, whey proteins make up about 5% of the

adsorbed protein and about 20% of the surface area covered;

for higher pressures, the proportion becomes increasingly

smaller (Sharma & Dalgleish, 1994). In commercial UHT

milk, about 25% of the droplet surface would still be coated

with MFGM (Lopez, 2005). The casein layer around fat

droplets appears thinner when milk is microfluidized rather

than regularly homogenized, suggesting micelle fragmenta-

tion (Dalgleish, Tosh, & West, 1996).

Observed differences depending on the sequence ofhomogenization and heating steps

The differences depending on the sequence of homogen-

ization and heating steps are rather controversial due to the

various treatments applied and to the sample preparation

procedure. Van Boekel and Walstra (1989) did not detect

whey proteins in the membrane of homogenized fat droplets

before the heating step. On the other hand, these proteins

associate to lipid droplets from 70 8C when denaturation

begins. Several reactions can take place: (i) interaction with

other denatured whey proteins, (ii) interactions with

k-casein on the surface of casein micelles in the skim

milk phase, (iii) interactions with k-casein located at the

exterior of the casein micelles adsorbed on the fat globule

surface, (iv) interactions with residual native MFGM

material, and (v) direct interaction with the fat droplet

surface. The availability of k-casein is crucial in these

different phenomena. In homogenized milk, the interface

between the adsorbed micelle fragments and the fat surface

is formed of non-k-caseins. Therefore, k-casein is exposed

on the outside, which favors interactions between whey

proteins and proteins at the interface (Dalgleish & Banks,

1991). When milk is homogenized then heated, less caseins

and whey proteins would be adsorbed onto the lipid droplet

surface than when milk is heated then homogenized (Lee,

1997). This is conflicting with the study of Sharma and

Dalgleish (1994) highlighting more whey protein–lipid

droplet membrane interactions when milk is homogenized

then heated, suggesting that the newly formed fat droplet

membrane offers more available binding sites for whey

proteins after homogenization than under its native MFGM

conformation.

Heat treatment at 80 8C (3–18 min) induces incorpor-

ation of whey proteins, particularly b-Lg, in the MFGM

(Lee & Sherbon, 2002). This implies increased membrane

protein concentration. The glycoproteins PAS-6 and PAS-7

(so-called lactadherin) would disappear and the linkage of

b-Lg to the MFGM could be due to disulfide bonds with

membrane proteins. Homogenization (two stages, 50 8C, 17

and 3.5 MPa) causes casein adsorption onto the MFGM, but

no whey protein adsorption if not associated to heat

treatment (Lee & Sherbon, 2002). The total protein amount

(caseins and whey proteins) at the MFGM is not

significantly different whether homogenization is performed

before or after heat treatment. In another study (Lee, 1997),


whey protein amount in the lipid droplet membrane

increases when milk is heated then homogenized. This

suggests that the k-casein–whey protein complexes formed

during heat treatment adsorb onto the newly formed

membrane during homogenization. Conversely, if heating

is performed before homogenization, then the proteins are

already denatured and are less prone to take part to

interactions at the fat droplet surface (Dalgleish & Sharma,

1993). The membrane of homogenized droplets is thus

thinner and globule aggregation is favored. Two-stage

homogenization limits this phenomenon (van Boekel &

Walstra, 1989). If heat treatment is performed prior to HPH

of skim milk (41–186 MPa), more micellar material and

b-Lg–k-casein complexes are displaced to the skim milk

phase (Sandra & Dalgleish, 2005); this would turn them

potentially available for adsorption at the fat interface if the

same occurred in whole milk but this hypothesis is not

justifiable to date.

Briefly, when heat treatment is performed prior to

homogenization: (i) whey proteins are denatured and

interact with the native proteins of the MFGM and the

micellar caseins, particularly k-casein, and (ii) the casein–

whey protein complexes adsorb onto the lipid droplet

interface. When homogenization is performed prior to heat

treatment: (i) the semi-intact casein micelles or micellar

fragments cover the fat droplet interface, and (ii) the

denatured whey proteins link to the native MFGM proteins

and adsorbed caseins via disulfide bonds. However, the

compositional changes in the fat droplet membrane

depending on the order of homogenization and heat

treatments do not seem to influence cream separation.

Cream separation is identical whether milk is (i) homogen-

ized, (ii) heated then homogenized, or (iii) homogenized

then heated, and always lower than for unhomogenized milk

(Hillbrick, Mcmahon, & Mcmanus, 1999; Lee, 1997). The

homogenization step can thus be performed prior to UHT

treatment, allowing lower asepsis rules and thus lower

industrial costs.

Current data related to homogenization effectson the health properties of milkTaste and digestion

A link exists between sensory stimulation and post-

prandial lipid metabolism (Mattes, 1996): the amount of

post-prandial plasma triacylglycerols after the ingestion of

oil capsules was measured in subjects exposed to various

oral stimuli masticated but not ingested. Higher plasma

triacylglycerols were observed in subjects in contact with

the fattest stimulus (cream cheese). Therefore, the sensory

properties homogenized vs unhomogenized milk could

affect the metabolic response. Due to increased photo-

chemical sensitivity and lipolysis, homogenized milk is

more sensitive to off-flavor formation during storage

(Humbert et al., 1980). Combined homogenization and

heat treatment also increase the viscosity of whole milk

(Lee, 1997). The possible sensory-stimulated effects of

these differences on milk digestion should be investigated.

During digestion of homogenized milk, a simultaneous

coagulation of caseins and lipid droplets occurs in the

stomach. The structure of coagulated matter is much finer

than for untreated milk and the protein transfer to the small

intestine is easier: for subjects suffering intestinal disease,

homogenized milk is more easily digestible than untreated

milk (Sieber, Eyer, & Luginbuhl, 1997). In minipigs, raw

milk and pasteurized milk give a very firm curd and present

slower gastric emptying rate than pasteurized homogenized

milk, UHT milk or cultured milk (Meisel & Hagemeister,

1984). Moreover, the proteolysis of casein is enhanced with

pasteurized homogenized milk and UHT milk (Pfeil, 1984).

UHT milk also results in a greater absorption in this animal

model (Kaufmann, 1984).

Regarding lipid digestion, the gastric step is crucial since

it facilitates subsequent triacylglycerol hydrolysis by the

pancreatic lipase (Fave et al., 2004). This is particularly

important in infants and in adult patients suffering

pancreatic insufficiency. In minipigs, Buchheim (1984)

found extended lamellar structures of mono-glycerides in

the gastric coagulum of pasteurized milk (homogenized and

non-homogenized) and of UHT milk, but only rarely in raw

milk and cultured milk, providing direct evidence for

lipolysis that occurs to a considerable extent in the former

milks. After feeding raw milk and (pasteurized and

homogenized) cultured milk, only slight gastric lipolysis

is observed in minipigs (Timmen & Precht, 1984). In

humans, the lipid droplet size is a key physico-chemical

factor governing fatty acid bioavailability: smaller droplets

result in greater lipolysis via their surface excess on a larger

interface area (Armand et al., 1999; Fave et al., 2004). The

small sized droplets in homogenized milk would thus favor

milk fat lipolysis. But in premature infants, human milk fat

globules (surrounded by a human native MFGM similar to

Fig. 1) result in a more efficient gastric lipolysis than the

much smaller homogenized lipid droplets of infant formula

(Fave et al., 2004). Human milk fat globules are larger in

colostrums (d32Z4.3 mm) than in mature breastmilk (d32Z3.5 mm), and much larger than infant formula droplets

(d32Z0.3 mm; Michalski, Briard, Michel, Tasson, &

Poulain, 2005). The ultrastructure of milk fat droplets

appears thus to be of utmost importance (Fave et al., 2004);

it can be related to the above-mentioned changes in

z-potential that could affect lipase access to the interface.

In rats, small homogenized fat droplets fed as a cream result

in a slower triacylglycerol metabolization than large

phospholipid-coated droplets or unemulsified fat

(Michalski, Briard, Desage, & Geloen, 2005; Michalski

et al., 2006). The slower metabolization can be linked to the

delayed gastric emptying due to the gastric clot structure,

even if small droplets are more efficiently lipolyzed. The

discrepancies with minipig studies can be due to the

different animal models and the different fat content of the

gastric clots. Long-term effects of these metabolization


differences compared with untreated milk fat globules

remain to be elucidated in humans.

Atherosclerosis and coronary heart diseaseIn atherosclerosis, arteries are partially or totally

obstructed due to the formation of plaques rich in

cholesterol at the internal face of the vascular wall. Along

time, clotting can occur, obstructing arteries and depriving

vital organs of oxygen. This is why it is advised to control

cholesterol level by limiting saturated fat consumption via

butter, milk and fat meat. However, the role of these foods

in promoting cardiovascular diseases is controversial. The

amount of absorbed cholesterol via dairy products con-

sumed daily only represents 15% of the daily recommended

cholesterol intake and the beneficial role of milk fat has

been highlighted in an in-depth review by Berner (1993b).

Studies that used single dietary fat sources to compare

effects of fats on blood lipids should be taken with caution

since the effects of any single fat source will be diluted when

in a mixed diet. The food energy intake as lipids should be

7.5% saturated fatty acids, 15% mono-unsaturated fatty

acids and 7.5% polyunsaturated fatty acids (PUFA). But

within one group, different fatty acids do not act the same

way, and the impact of milk products on plasma lipids and

on the risk of cardiovascular disease is different from

expected considering their lipid content and composition

(Berner, 1993b).

Atherosclerosis develops during the post-prandial lipe-

mia stage and some studies have recently shown that

different structured dairy products result in different lipemia

profiles. Consequently, it is not justified to qualify milk as

anti- or pro-atherogenic regarding solely its lipid compo-

sition. Milk, mozzarella–cheese and butter in test meals do

not result in the same timing of triacylglycerol peak in type

II diabetic patients (Clemente et al., 2003). Fermented milk

results in a slower gastric emptying rate than regular milk

(certainly both homogenized although not stated), and in a

greater increase and a quicker decrease of the triacyl-

glycerol content in all lipoprotein fractions (Sanggaard

et al., 2004). Controlled dietary studies in humans have

shown no difference in the effect on plasma cholesterol of

milk and butter with equal fat content and adjusted

regarding lactose and casein content (Tholstrup, Høy,

Normann Andersen, Christensen, & Sandstrom, 2005). In

a careful review, Tholstrup (2006) concludes that there is no

strong evidence that dairy products (i.e. including hom-

ogenized milk) increase the risk of coronary heart disease in

healthy men of all ages or young and middle-aged healthy

women. Overall, studies would be needed in humans to

investigate the effect of homogenization on the anti- or pro-

atherogenic properties of milk.

Oster (1972) hypothesized that BXO released from the

MFGM due to homogenization would favor atherosclerosis.

The role of BXO in the generation of reactive oxygen

species in the cardiovascular system was also emphasized

(Berry & Hare, 2004). However, the former hypothesis is

criticized on many grounds such as the inactivation BXO at

the acidic gastric pH (Mangino & Brunner, 1976). The

possibly harmful effects of BXO have finally been the

subject of questions to the European Parliament in

September 2000 and April 2001 (written questions

E-2907/00 and E-0864/02). In both cases, the Commission

responded (i) not to have sufficient proofs regarding harmful

enzyme effects and (ii) not to consider new labelling rules.

Today, even if this hypothesis is often discussed, the

possible atherogenic role of BXO enhanced by homogen-

ization appears to be rejected by the scientific community.

Coronary diseases are due to the development of

arteriosclerosis in coronary arteries (arteries that bring the

oxygen necessary for the heart to the myocardium).

Arteriosclerosis is characterized by the deposit of more or

less calcified plaques in the internal wall of coronary

arteries. Gradual narrowing (stenosis) of arteries results,

possibly until their final destruction. Some casein-derived

peptides present anti-thrombotic and anti-hypertensive

features; e.g. the k-casein fragment f103–111 can prevent

blood clotting through inhibition of platelet aggregation

(Silva & Maltaca, 2005). Also, recent studies point out that

(i) milk drinking may be associated with a small but

worthwhile reduction in heart disease and stroke risk

(Elwood, Pickering, Hughes, Fehily, & Ness, 2004; even

though the definition of ‘milk intake’ presents some

difficulties, Tholstrup, 2006), and (ii) milk product intake

is negatively associated with cardiovascular disease risk

factors (Warensjo et al., 2004). Overall, no unfavorable

effect of dairy product could be found in these studies

involving the consumption of heat-treated and homogenized

milk. Since, these treatments involve the reorganization of

casein components (especially k-casein) within the milk

structure, one could suggest that the effect of milk

processing factors should be examined in respect with the

desirable bioactivity of casein-derived peptides.

On the other hand, Moss and Freed (2003) recently

studied the link between coronary disease occurrence and

circulating antibodies against the MFGM proteins. The

latter might by atherogenic by causing the aggregation of

lymphocytes and platelets. However, Spitsberg (2005)

criticizes this suggestion on analytical grounds. Besides,

we should stress that some populations, such as in the

French region of Brittany, use to consume high amounts of

buttermilk that is rich in MFGM fragments, while they are

not associated with the highest coronary mortality within

Northern France (Oberlin, Moquet, & Folliguet, 2004).

Also, hard cheese consumption is negatively correlated with

coronary heart disease (Moss & Freed, 2003; Tholstrup,

2006), although this product is rich in MFGM. Though, we

should highlight that buttermilk and hard cheese are

manufactured from unhomogenized milk. Since, homogen-

ization changes the organization of the MFGM and the

exposure of its proteins, this treatment might trigger the

putative atherogenic effect of these proteins. Studies are

needed to elucidate this point.


Finally, the A1 variant of b-casein in cow’s milk yields

b-casomorphin 7 (Jinsmaa & Yoshikawa, 1999), a bioactive

peptide with the ability to catalyze the oxidation of LDL that

is implicated in the cardiovascular risk (Allison & Clarke,

in press). The issue of the A1-b–casein variant effect on

coronary heart disease appears to be highly controversial

(Truswell, 2005; Woodford, 2006). Since homogenization

has an effect on milk structure, particularly regarding casein

distribution, we should wonder whether milk processing has

an impact on the possible role of A1-b-casein in coronary

heart disease.

Lactose intolerance and milk allergyLactose intolerance results from a lack of lactase

necessary for its proper digestion. Delayed gastric

emptying has been proposed as one possible explanation

for improved lactose tolerance after ingestion of milk with

a meal instead of milk on its own (Vesa, Marteau, &

Korpela, 2000) but no clear conclusion can be drawn

(Korhonen & Korpela, 1994; Vesa et al., 2000). Paajanen,

Tuure, Poussa, and Korpela (2003) studied adults tolerant

to lactose, with a subjective tolerance to unhomogenized

milk but describing subjective intolerance to homogenized

milk. This study revealed no symptom difference between

homogenized and unhomogenized milk consumers. A

following study dealt with adults intolerant to lactose

(Korpela, Paajanen, & Tuure, 2005). No significant

difference is observed in the symptomatic response

between unprocessed organic milk and processed milk.

Even though some subjects subjectively experience a better

tolerance of unhomogenized than homogenized milk, this

is not the case in lactose intolerant subjects in general

(Korpela et al., 2005).

Cow’s milk protein allergy (CMPA) is an abnormal

reaction of the immune system to proteins contained in

cow’s milk. The incidence of allergy in early childhood is

2–3% (Host, 2002). The major allergizing proteins are b-Lg,a-La and caseins, causing anaphylactic reactions (immune

phenomena induced by a type I hypersensitivity reaction to

the IgE mediation). Decreasing levels of milk-specific IgE

might signify allergy resolution. In animal models,

homogenization seems to favors hypersensitivity. Hom-

ogenization and pasteurization enhance the humoral

immune response of rats charged intraperitoneally with

milk (Feng & Collins, 1999). Homogenized milk orally fed

to hypersensitive mice induces an anaphylactic chock

(Poulsen & Hau, 1987), increases milk-specific IgE

production (Nielsen, Poulsen, & Hau, 1989), increases the

mass of intestinal segment and induces mastocyte degranu-

lation (Poulsen, Nielsen, Basse, & Hau, 1990). Moreover,

the allergenicity of homogenized milk in mice increases

with increasing fat content (Poulsen, Hau, & Kollerup,

1987). On the other hand, unhomogenized cow’s milk

induces few or no such symptoms and immune responses.

However, when milk is given intravenously (Poulsen &

Hau, 1987) or subcutaneously (Poulsen et al., 1990), the

same reactions are observed regardless of milk treatment.

In Northern countries, many consumers and also parents

of allergic children state that they tolerate untreated cow’s

milk and pasteurized non-homogenized milk, conversely to

homogenized milk. The explanation could be that during

homogenization, the milk fat presents a dramatically

increased surface onto which allergenic milk proteins

adsorb. In untreated milk, many of the antigenic proteins

are located inside casein micelles. In homogenized milk, the

amount of exposed antigenic proteins increases (Poulsen &

Hau, 1987). Besides, there is also some release of MFGM

proteins (listed in Table 4) in the aqueous phase (the latter

were suggested to be potential allergens, though with no

clear-cut evidence, in a viewpoint by Riccio, 2004).

However, the amount and exposure of allergenic proteins

in untreated milk appear to be sufficient to induce allergic

reactions in some subjects. Moreover, clinical studies reveal

no difference between homogenized and unhomogenized

milk in children allergic to milk (Host & Samuelsson, 1988)

or in adults intolerant to lactose or hypersensitive to milk

(Pelto, Rantakokko, Lilius, Nuutila, & Salminen, 2000). In

one study, homogenized pasteurized milk was found less

suitable than unhomogenized milk in 10% of the children

subjects with milk protein allergy (Hansen, Host, &

Osterballe, 1987). But few studies concern subjects with a

better milk tolerance. No difference was found in the

immunological responses to homogenized and unhomogen-

ized milk in healthy adults with a good tolerance of milk

(Paajanen, Tuure, Vaarala, & Korpela, 2005). Accordingly,

a recent review points out that homogenization does not

change the allergenic potency of cow’s milk (Paschke &

Besler, 2002). However, Paajanen et al. (2005) point out the

possibility that homogenized and unhomogenized milk

could induce different types of primary immunization to

cow’s milk antigens in immunologically intact individuals,

i.e. in infants. Moreover, most milk proteins, even minor

proteins, are potential allergens (Wal, 2004). This can

explain why the effect of homogenization may be difficult to

observe, since individuals can be sensitive to various

epitopes and since some human groups can be more

sensitive than others. The available evidence is not sufficient

to predict reliably the effect of food processing on allergenic

potential of milk proteins (Wal, 2004).

Food processing and interactions between constituents

and additives are strongly suspected to be responsible for at

least part of the increase of allergy incidence (Sanchez &

Fremont, 2003). Heating may have no effect or it may

decrease or increase allergenicity. Even in the absence of

heating, interactions between proteins and other com-

ponents of food can cause conformational changes in

allergens, thereby affecting their thermal stability. The

effect of such interactions on the allergenicity of proteins is

practically unknown today (Sanchez & Fremont, 2003). The

most important consequence of heating at common milk

processing temperatures seems to be the increased

Table 4. Major proteins and other components of the bovine MFGM, according to the nomenclature proposed by Mather (2000), withclaimed functions and health effects (benefits: C, or adverse effects: K)

Proteins Mw (kDa) Function Health effect

Mucin 1 (MUC1) (glycoprotein) O160a, 50–500b Protects from physical damage andinvasive pathogensb

?

Butyrophilin (BTN) (glycoprotein) 56b–66a Milk fat globule secretion Belongs to immunoglobulinsb

(K) Induces or modulates experimentalallergic encephalomyelitisb

(C) Suppression of multiple sclerosisa

Xanthine oxidase (XDH/XO) 150a Structural, lipid secretiona (C) Bactericidal agenta

Role in purine metabolismb (K) Risk factor for coronary heartdisease?b

Cluster of differentiation (CD36)(glycoprotein)

53b–78a Fatty acid transportera ?Macrophage markerb

Phagocytosis by neutrophilsb

Fatty acid binding protein (FABP) 13b–15a Fatty acid metabolism (C) Cell growth inhibitora

Increase of lipid droplets in thecytoplasmb

(C) Anti-cancer factor (as a seleniumcarrier)a

(K) Similar to P2 myelinprotein involved in experimental allergicneuritisb

BRCA1 210 Cancer suppressora (C) Inhibition of breast cancer (alsoBRCA2)a

Lactadherin (PAS 6/7) 43–59b Belongs to cadherinsb

Calcium-dependent adhesive prop-ertiesb

Role in the epithelialization, cellpolarization, cell movement andrearrangement, neurite outgrowth,synaptic activity in the central nervoussystemb

Phospholipid bindingb (C) Protection from viral infection inthe gutb

Adipophilin (ADPH) 52b Uptake and transport of fatty acidsand triacylglycerols

?

Other components Health effect

b-Glucuronidase inhibitora (C) Inhibition of colon cancera

Helicobacter pylori inhibitora (C) Prevention of gastric diseasesa

Cholesterolemia-lowering factora (C) Anti-cholesterolemica

Vitamin E and carotenoids (C) Anti-oxidantsa

Phospholipids (C) Inhibition of colon cancera

(C) Anti-cholesterolemica

(C) Suppression of gastrointestinal pathogensa

(C) Anti-Alzheimer, anti-depressant, anti-stressa

Phosphoproteins (C) Source of organic phosphorus and Ca-phosphatea

a Spitsberg (2005).b Riccio (2004).


immunoreactivity (capacity to bind IgE) of some milk

allergens (Besler, Paschke, & Paschke, 2001). This can be

due to epitope exposure after conformational changes or to

changes in aminoacids due to Maillard reactions with sugars

enhanced by heating (Sanchez & Fremont, 2003). Protein–

fatty acid interactions can also change the secondary

structure of b-Lg upon heating or even at room temperature

with oleic acid (Ikeda, Fogeding, & Hardin, 2000). Since

some b-Lg can be present at the lipid interface in

homogenized milk, such interactions can occur and their

effect on protein allergenicity should be investigated,

independently from heat treatments.

DiabetesType I diabetes is an auto-immune disease initially

characterized by the infiltration of Langerhan’s islets by

macrophages and lymphocytes. Consequently, the insulin

producing cells (pancreatic b-cells) are selectively

destroyed, causing an absolute and definitive insulin

deficiency. Dietary factors such as milk consumption have

been discussed as being involved (Schrezenmeir and Jagla,

2000): 50% of type I diabetics consumed cow’s milk before

the age of 3 months (Kostraba et al., 1993). The risk of type

I diabetes is higher for children who were breast fed less

than 4 months and who received cow’s milk at younger than


5 months and interactions between these factors are

important (Sipetic, Vlajinac, Kocev, Bjekic, & Sajic,

2005). Early exposure to cow’s milk is not associated with

increased risk of type I diabetes development in low risk

subjects. However, cow’s milk is suspected to be a risk

factor in subjects genetically prone to diabetes (Dahl-

Jorgensen, Joner, & Hanssen, 1991; Fava, Leslie, &

Pozzilli, 1994) even if this was not confirmed by the study

of Meloni et al. (1997). Karjalainen et al. (1992)

hypothesized that a particular region of BSA (a 17-residue

peptide called ABBOS) would be the reactive, trigger

epitope for genetically prone subjects. Heating milk above

85 8C would be sufficient to denaturate BSA, more

specifically its reactive epitope regarding type I diabetes

(Strand, 1994). More recently, the implication of A1-b-casein in type I diabetes incidence was suggested (Elliott,

Harris, Hill, Bibby, & Wasmuth, 1999). Truswell (2005)

rules out the hypothesis of different effects of A1 and A2

variants of b-casein; however, his viewpoint is criticized

(Allison and Clarke, 2006; Woodford, 2006): studies often

fail to provide a true control devoid of diabetogenic effects.

Schrezenmeir and Jagla (2000) point out the need for

intervention studies in humans, and particularly, what

impact consumption of cow’s milk has beyond infancy.

Studies usually deal with the consumption of commercial

homogenized milk. Further studies appear to be necessary to

finally state whether cow’s milk consumption is linked to

type I diabetes development and examine the impact of

homogenization in this respect.

In contrast to type I diabetes, the etiology of type II

diabetes is still unclear. It is part of the so-called

metabolic syndrome, which besides diabetes comprises

abdominal obesity, hypertension, dyslipoproteinemia and

precocious atherosclerosis. Type II diabetes is character-

ized by the insulinoresistance of peripheral tissues

associated with hyperinsulinemia, followed by the

secondary qualitative and quantitative deficiency of

pancreatic insulin secretion due to glucose (Schrezenmeir

& Jagla, 2000). The early stage of type II diabetes is

characterized by insulinoresistance of peripheral muscular

and adipose tissues. Insulin resistance usually corresponds

to the reduced hypoglycemic effect at a usually efficient

concentration. High saturated fatty acid consumption is

associated with glucose intolerance or insulin resistance

and type II diabetes. Now, milk contains 60–70 g of

saturated fatty acids per 100 grams of total fatty acids. On

the contrary, unsaturated fatty acids (30–35% of total fatty

acids) are inversely associated to diabetes risk (Mann,

2002), and milk also contains beneficial minor com-

ponents such as CLA (Schrezenmeir & Jagla, 2000).

Epidemiological data about a relationship between milk

consumption and type II diabetes are rare (Schrezenmeir

& Jagla, 2000); moreover, milk processing parameters are

not controlled. Randomized controlled trials are required

to establish whether milk avoidance is causally associated

with the lower occurrence of type II diabetes observed in

non-milk consumers (Lawlor, Ebrahim, Timpson, &

Davey Smith, 2005) and the effect of milk processing

parameters should be examined.

Other health effects linked to the milk fat globulemembrane components

Proteins and other components of the native MFGMwere

found to present various health effects, listed in Table 4.

Riccio (2004) claims that MFGM proteins could possibly be

involved in autoimmune and neurological diseases, such as

multiple sclerosis and autism. Butyrophilin, the main

MFGM protein, shows more than 50% amino-acid

homology with a corresponding domain of the myelin

oligodendrocyte glycoprotein (MOG). The latter is a minor

component of the myelin membrane in the central nervous

system. MOG induces experimental allergic encephalomye-

litis (EAE), related to human multiple sclerosis, in many

experimental animals (Riccio, 2004). Spitsberg (2005)

reviewed recent studies demonstrating that butyrophilin

can trigger the development of EAE or suppress the disease.

The treatment of specific mice with butyrophilin either

before or after immunization with MOG prevents or

suppresses the clinical manifestation of EAE, suggesting

that the consumption of dairy products enriched with

MFGM could modulate the pathogenic response to MOG

in a positive direction. Riccio (2004), however, points out

that butyrophilin induces inflammatory responses in the

central nervous system when injected alone into animals.

This author advises cautious removal of MFGM from dairy

products. On the contrary, the thorough review by Spitsberg

(2005) highlights many health benefits of MFGM com-

ponents such as: (i) anti-cancer effects via the absorbed

peptides from proteins FABP and BRCA1, the b-glucuroni-dase inhibitor and the phospholipids (mainly sphingomye-

lin), (ii) anti-cholesterolemic effects mainly via

phospholipids, (iii) prevention of gastric diseases via

sialyated glycoproteins. This author suggests the use of

MFGM as a potential nutraceutical. The issue of MFGM

components contributing to health and disease still appears

controversial.

Due to the physical stress caused by homogenization, a

rearrangement of the MFGM components occur and some

fragments are released to the aqueous phase, while in whole

milk the MFGM is native at the globule surface (Fig. 1).

Due to its lipophilicity, butyrophilin should remain at the

lipid interface. It would be important to investigate the

effect of MFGM fragments on the above-mentioned health

effects when dispersed in an aqueous phase or adsorbed at a

lipid interface. Indeed, changes in the physico-chemical

arrangement of bioactive molecules may affect their activity

and suggest different effects of unhomogenized and

homogenized milk in this respect.

ConclusionChanges caused by homogenization on milk organization

were broadly investigated. The size of milk fat globules


dramatically decreases and caseins become the main protein

fraction adsorbed onto the newly formed interface, together

with some whey proteins. Heat treatment changes the

impact of homogenization on milk structure. When milk is

heated then homogenized, complexes of caseins with heat-

denatured whey proteins adsorb onto the new expanded

lipid droplet interface. When milk is homogenized then

heated, heat-denatured whey proteins link to the proteins

already located at the homogenized droplet interface

(MFGM proteins and casein micelles or fragments thereof).

There are much less studies dealing with the impact of

homogenization and milk processing in general on the

human health properties of milk. Homogenization seems to

improve milk digestibility for subjects suffering intestinal

disease, however, infants digest better native human milk fat

globules than homogenized droplets from infant formula.

Presently, there seems to be no strong evidence that dairy

products, including homogenized milk, increase the risk of

coronary heart disease in healthy men of all ages or middle-

aged healthy women. Moreover, some casein peptides

present anti-thrombotic and anti-hypertensive features, and

milk drinking might be associated with a small reduction of

stroke risk. Though, the effects of milk homogenization and

heating regarding the bioactivity of casein peptides and the

cardiovascular impact of milk consumption should be

elucidated. Studies found to date do not show any impact

of homogenization on milk allergy or intolerance in

humans, except for a few percent of children allergic to

milk who would tolerate less homogenized milk. However,

differences of primary immunization could be much more

important in infants since most milk proteins are potential

allergens, especially when heated. Early exposure to cow’s

milk in genetically prone children could also be a risk for

type I diabetes but this result still seems controversial.

Studies are also required to establish whether milk

avoidance is causally associated with the lower occurrence

of type II diabetes observed in non-milk drinkers. The

impact of homogenization in the latter results has not been

investigated. A role of A1-b-casein is presently suspected intype I diabetes and coronary heart disease. Some authors

also claim that MFGM proteins could be atherogenic and

implied in autoimmune and neurological diseases. How-

ever, many other studies highlight beneficial health effects

of MFGM components that could be used in the prevention

of cancer, gastric diseases or hypercholesterolemia. The

distribution and conformation of caseins and MFGM

proteins changes in homogenized milk, which could alter

or enhance their bioactivity and allergenicity, as well as

those of other components of health interest.

The structure of milk is greatly altered depending on

the various mechanical and thermal steps of the

processing chain. Studies dealing with the health proper-

ties of milk and other dairy products should use samples

whose physico-chemical properties are well character-

ized. In the current context of obesity and allergy

outbreaks, interdisciplinary studies on the impact of

processing parameters on the nutritional and health value

of milk appears to be a challenging and necessary

research area for the future.

AcknowledgementsThe authors thank the steering committee for Nutrition of

Arilait Recherches for undertaking and financing this

literature review. M. Armand, D. Dalgleish, F. Guyomarc’h

and H. Vidal are acknowledged for their critical comments

on the manuscript. In a discussion of many health research

studies, some works were cited indirectly through reviews.

The authors apologize to those not cited.

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