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Summer 2009 #22


Providing scientific information to professionals in health and nutritional foods,
focused on the benefits of milk components

The role of
milk components
on skin health

Introduction
SKIN
Composition of skin
Roles of skin
Skin aggression factors
Skin disorders: risk factors

Milk components
and skin disorders
Vitamins and minerals
from milk
Specific proteins
and peptides from milk
Lipids and phospholipids
from milk
2

Conclusion

Human skin is the largest organ of the body (Furukawa et al., 2008) and has the particularity to be in
perpetual interaction with environmental factors (Dubertret, 2000). Thus, it is important to know and
understand its structure and roles, as well as its factors of aggressions. Some micronutrients, proteins
or peptides from milk have demonstrated beneficial effect in some skin disorders.

SKIN

The most important function of skin is to form an effective barrier between the inside and
the outside of the organism.

1.1

Composition of skin

The thin structure of skin shows considerable regional


variations, concerning its thickness (varying from 1 to 4 mm),
the distribution of epidermal appendages and the density
of melanocytes. Skin is organized in three layers including
from top to bottom (Figure 1):
Epidermis or stratum corneum, which is mainly constituted
from keratinocytes (90-95%).
Dermis or corium, which is the intermediate layer. It is
a supportive, compressible and elastic connective tissue
protecting the epidermis. Its thickness varies considerably
with the anatomic location.
Hypodermis, which is the deepest layer, is a fatty tissue,
mainly composed of adipocytes (Kankatis, 2002).

Summer 2009 #22

Figure 1: Skins structure


(adapted from Brouard and Barrandon, 2003)

In addition to these layers, three epidermal appendages


have been identified and are necessary for the good health
and function of skin: sebaceous glands, hair follicles and
sweat glands (Man et al., 2009).

Skin helps to:


protect against
aggressions,
regulate body
temperature,
synthesize
vitamin D,
sensory function.

Three types of
aggressions:
Physical
Chemical
Biological

1.2

Roles of skin

Skin mainly provides six roles for the good


functioning of the organism. First, it protects
against aggressions (this part is more developed
below). Then, it is able to regulate body temperature
(Blanpain and Fuchs, 2009; Kantakis, 2002).
This involves not only a transepidermal water
regulation that induces a good hydration of skin
(Jung and Stingl, 2008) by the presence of natural
hygroscopic agents within the corneocytes and the
skin cornea intercellular lipids orderly arranged
(Verdier-Svrain and Bont, 2007), but also a
very abundant capillary system which also has

1.3

a nutritive role (Ambrozy et al., 2009). Moreover,


skin exerts an important sensory function via
the nervous system (Boulais and Misery, 2008).
Besides, skin is able to synthesize vitamin D
(Holick, 2008; Tukaj, 2008), when it is exposed
to the sunlight. This represents an important role
as vitamin D is necessary for a lot of functions
in the organism, like bone mineralization (Holick,
2008; Tukaj, 2008). Skin vitamin D synthesis
can represent up to 90% of the total amount
(Tukaj, 2008).

Skin aggression factors

The main role of skin is to protect the organism against biological, mechanical, and physical aggressions,
as it is represented in figure 2 (Proksch et al., 2008). Depending on the environmental aggressions,
skin is able to develop a proper mechanism of defense. For instance, in case of light aggressions, skin
is able to secrete melanin, a pigment which can protect skin cells from UV radiations. In case of rubs,
skin is also able to develop callosity (Dubertret, 2000).
Here three types of aggressions can be distinguished
(Dubertret, 2000):
Physical aggressions: There are two types of
physical aggressions: mechanical and light. For
the first, it is mainly the dermis which ensures
this function due to its high content in collagen
and elastin which induce its good resistance. For
the second, in response to sun exposure, skin
is able to synthesize melanin by photoprotective
cells from UV exposure (Miyamura et al., 2007).
Chemical aggressions: Skin is able to prevent
the penetration of chemical substances thanks to
its low permeability. In addition, this permeability
can regulate gas exchange in the organism.
Biological aggressions: Skin possesses immune cells which are able to counteract the invasion
of micro-organisms. These are the Langerhans
cells, which are the equivalent of macrophages.
It seems that skin can induce potent immune
responses.

Risk factors
of skin
disorders

1.4

Skin disorders: risk factors

A lot of factors can contribute to skin disorders:


environment, allergy, stress (Kie-Swierczyska et
al., 2006; Schmitt et al., 2008), heredity (Chang et al.,
2008), deficiency of micronutrients (El-Gilany
and Fathy, 2009; Zablotska et al., 2008), personal
hygiene (El-Gilany and Fathy, 2009; Wu et al.,
2007), diabetes (Van Hattem et al., 2008), smoking

Summer 2009 #22

Figure 2: Barrier function of skin


(adapted from Proksch et al., 2008)

(Huerta et al., 2007), sun exposure (Chang et al.,


2008), being overweight (Chang et al., 2008)...
It is difficult to define all the risk factors,
because it depends on the skin diseases. If there
is an alteration of one of the three types of defense
mechanism against aggressions described above,
that can be also considered as a risk factor.

Milk components and skin disorders

Which milk components can play a role in the improvement of skin disorders?
Milk is mainly composed of water (about 87%). The other 13% consist of carbohydrates
with lactose, lipids with saturated, mono-unsaturated and poly-unsaturated fatty
acids, and proteins like caseins and whey proteins. Moreover, milk is an important
source of micronutrients, necessary for the infant development. Beside fat-soluble
and water-soluble vitamins, minerals and trace elements are also present in milk.

A lot of vitamins
and minerals
present in milk
have an interest
in skin health

2.1

Vitamins and minerals from milk

Among the different micronutrients that have been


identified, some are recognized for their usefulness
in skin health, as for instance vitamin B12, which,
in topical application, seems efficient on atopic dermatitis, and on vitiligo when combined
with vitamin B9 (Stcker et al., 2004; Shaker
and El-Tahlawi, 2008; Juhlin and Olsson, 1997).
Concerning vitamin B9, it seems to have beneficial
effect for psoriasis and others skin diseases (Gisondi et al., 2007). In an observational study, in
4025 women, the vitamin C supplementation was
correlated to a reduction of the cutaneous dryness
and of the wrinkled appearance of skin (Cosgrove
et al., 2007). Moreover, vitamin C, combined with
madecassoside, could ameliorate the clinical
score for deep and superficial wrinkle suppleness,
firmness, roughness and skin hydration (Haftek
et al., 2008). Fat-soluble vitamins, such as vitamin A,
present some interests for skin applications.
Indeed, retinol is mainly used for its anti-ageing
properties by topical administration (Bertin et al.,
2008; Mukherjee et al., 2006; Kafi et al., 2007;
Sorg et al., 2006; Carlotti et al., 2006).

2.2

Trace elements and minerals have demonstrated


also some beneficial effects for skin health. For
instance, zinc is well recognized for its antiinflammatory properties for acne (Dreno et
al., 1989) and for its wound healing property
Lansdown et al., 2007). Then, manganese, an
important antioxidant, in theform of a manganese
peptide complex showed a beneficial effect in the
treatment of photodamaged skin, by improving
signs of cutaneous photodamage (Hussain and
Goldberg, 2007). Another trace element, copper,
proves its wound healing action in rabbits in a
topical tripeptide complex form (Gul et al., 2008;
Cangul et al., 2006).
Nevertheless, the amounts of the above-mentioned
micronutrients in the milk are too small to have
individually an effect on skin health. But all
together, in combination with milk proteins, they
could contribute to the good health of skin.

Specific proteins and peptides from milk

Cows milk is a member of the so-called Big-8


food allergens (Crittenden and Bennett, 2005;
Meyer, 2008). This allergy is the most frequently
reported during infancy (Crittenden and Benett,
2005), mainly due to beta-lactoglobulin, casein,
alpha-lactalbumin and seroalbumin (Avila Casta
et al., 2005). This allergy can be manifested by skin
reactions as atopic dermatitis, erythematous rash,
urticaria or angio-odema for instance (Martorell
et al., 2008; Brill, 2008). In addition, some

epidemiological studies hypothesized that there is


a positive association between milk consumption
and acne in teenage boys and girls in general
(Adebamowo et al., 2008; Adebamowo et al.,
2006; Adebamowo et al., 2005).
Nevertheless, various beneficial effects on skin
disorders have been demonstrated for the specific
proteins and peptides isolated from milk, as
presented hereafter.

Alpha-lactalbumin
and Alpha
S1-casein can
reduce stress &
anxiety that are
two of risk factors
of skin disorders

1. Anti-stress action: reduction of a risk factor of skin disorders


Stress has been shown to be an important factor involved in skin disorders such as pruritus (PogatzkiZahn et al., 2008), psoriasis vulgaris (Chang et al., 2008; Ionov, 2009; Janowski and Pietrzak, 2008;
Malhotra and Mehta, 2008), scleroderma (Chen et al., 2008), allergic skin diseases (Kie-Swierczyska
et al., 2008), lichen planus (Krasowska et al., 2008), atopic eczema (Schmitt et al., 2008), rosacea
(Jaworek et al., 2008).
Here, two milk proteins which demonstrated their effectiveness against stress and anxiety have been identified:
Alpha-lactalbumin
Alpha-lactalbumin showed anti-bacterial, antitumoral and anti-stress properties. An alphalactalbumin enriched diet is considered as
anxyolitic (Zimecki and Artym, 2005; Zimecki and
Kruzel, 2007). These properties have been demonstrated in 4 clinical trials, 3 of them deals with stress
induced or depressed people (Markus et al.,
2002; Merens et al., 2005; Markus et al., 2000)
and one concerns healthy women (Scrutton et al.,
2007). Three clinical trials in healthy women and
in high-stress vulnerable people obtained positive
results, whereas the last one did not demonstrate
any efficacy because of the inadequacy of dose
or duration.
Alpha-S1-casein
Only two clinical trials have been identified
to measure the anti-stress properties of alpha
S1-casein in healthy human volunteers facing
successive mental and physical stress situations and in stress-related women symptoms
(Messaoudi et al., 2005; Kim et al., 2007). Results
of the 2 trials were positive with an improvement on
stress-related symptoms.

Figure 3: Mechanism of action of alpha-lactalbumin


on stress and anxiety

2. A
 nti-fungal and anti-viral actions
Lactoferrin can
reduce the
Herpes Simplex
Virus 1 and 2
Alpha-lactalbumin,
associated
with oleic acid,
can reduce
the lesions
of skin
papillomas

Lactoferrin

The combination alpha-lactalbumin - oleic acid

Lactoferrin is an iron-binding protein from milk.


A recent review reported that lactoferrin facilitated
the cure of dermatophytosis and decreased fungal
abundance in the skin of guinea pigs. Research also
demonstrated the beneficial effects of oral bovine
lactoferrin in other animal infections models,
including herpes virus skin infection and oral
candidiasis (Tomita et al., 2009). Lactoferrin has
been demonstrated as having antiviral activity
against Herpes simplex virus-1 and -2 (Marchetti
et al., 2009; Ammendolia et al., 2007). In addition
to interfering with viral entry, bovine lactoferrin
interfered the Herpes Simplex Virus-1 replication
by delaying the viral trafficking towards the nucleus
(Marr et al., 2009).

A randomized, placebo-controlled, double-blind


study demonstrated that alpha-lactalbumin, in
combination with oleic acid, is more efficient
than a placebo (saline solution) in 20 people
suffering from skin papillomas. The solutions were
administered topically for 3 weeks. The results
of this first phase indicated a reduction of the
lesion volume for the active group. After 2 years
of treatment, all lesions disappeared for 83% of
the subjects (Gustafsson et al., 2004).

A specific
whey protein
extract can
significantly
improve the
psoriasis
symptoms

3. A
 nti-psoriasis action
Whey protein fraction enriched
with growth factors
Two double-blind, placebo-controlled, randomized
studies and one open-label trial have been carried
out to assess the effect of a whey protein extract. The
most recent study, in 16 persons suffering from mild
to moderate psoriasis, demonstrated that 800 mg of
this whey protein extract for 56 days significantly improved the Dermatology Life Quality Index and the
Psoriasis Area and Severity Index scores (p<0.05)
at the end of the study (Drouin et al., 2008). The
previous trials have demonstrated the efficacy of this
whey protein extract at a more important dose (5g
per day for at least 56 days) in people with mild to
moderate psoriasis too (Poulin et al., 2007; Drouin et
al., 2007; Poulin et al., 2006; Poulin et al., 2005). All
these studies showed that this whey protein fraction
significantly improved the symptomatic scores of psoriasis and the quality of life of the participants.

4. W
 ound healing actions
Mitogenic Bovine
Whey proteins can
improve wound
healing
Alpha-Lactalbumin
can reduce
oxidative stress.
Suppressing
oxidative stress
can accelerate
wound healing
process

Day 1

Mitogenic bovine whey proteins


A clinical trial, on people suffering from chronic leg
ulcers, demonstrated that a topical application of
mitogenic bovine whey extract significantly decreased
the levels of matrix metalloproteinases-2 and -9
compared to the placebo group and also stimulated
wound healing (Valerias et al., 2006). These results
reinforced the in vivo study in which the mitogenic
bovine whey extract promoted the closure of excisional wounds in rat skin (Rayner et al., 2000).
Alpha-lactalbumin,
a whey protein rich in cystein
On the one hand, recent research on animal models
showed that alpha-lactalbumin, a whey protein rich
in cystein, reduces oxidative stress by its ability to
increase glutathione levels in the organism (Blouet
et al., 2007; Mariotti et al., 2004). However, this
antioxidant effect depends on denaturation or partial
hydrolysis of the protein (Clausen et al., 2009).

2.3

Figure 4: Representative picture of body lesions during


a study where a patient received whey protein extract
(800 mg per day) for 56 days.
Drouin R, Moroni O, Cantin K, Juneau C. A double-blind, placebocontrolled, randomized trial of XP-828L (800 mg) on the quality of
life and clinical symptoms of patients with mild-to-moderate psoriasis.
Altern Med Rev. 2008 Jun;13(2):145-52.

On the other hand, oxidative stress can modulate


wound healing (Rojkind et al., 2002). It has been shown
that suppressing oxidative stress may accelerate
this process (Tie et al., 2009; Shetty et al., 2008).
Indeed, although small amounts of reactive oxygen
species (ROS) are necessary for the process of
wound healing, an excess of ROS is deleterious
for wound repair. As a reduced level of glutathione
was reported in wounded skin of rats, enhancing
the level of this endogenous low molecular weight
antioxidant may improve wound healing (Schfer
and Werner, 2008). Like vitamin E (Musalmah et
al., 2005), glutathione also demonstrated its ability
to improve wound healing in vivo: topical application
of glutathione accelerated the process (Mudge et
al., 2002). Thus, by its ability to reduce oxidative
stress, alpha-lactalbumin may indirectly accelerate
wound healing. Nevertheless, the direct correlation
between alpha-lactalbumin supplementation and
wound healing has never been studied.

Lipids and phospholipids from milk

The composition and content of lipids in milk depend of


the mammalian species. The major fatty acids present
in milk include triacylglycerides, diacylglycerides,
saturated and polyunsaturated fatty acids, and
phospholipids. Bovine milk fat is especially composed
of saturated fatty acids (German and Dillard, 2006).
Phospholipids are present at the level of 1% of total
lipids and 0,03-0,04 % of milk (Haruta et al., 2008).
Lipids are one of the main components of creams
and others cosmetics for skin. Few studies have

Summer 2009 #22

Day 56

been performed on milk fat and skin applications.


However, one in vivo assay investigated the effect of
phospholipids concentrate from bovine milk (per os)
on mice. It was found that this fat fraction improves
significantly epidermis hydration, reduces transepidermal water-loss and modifies the epidermis
composition (increase of ceramides). All these
phenomena contribute to e hance the skin function
(Haruta et al., 2008).

Conclusion
Cows milk, and particularly proteins of milk, belongs
to the first allergen of food, which manifested itself by
atopic dermatitis for instance. However, some macro and
micro-nutrients from milk demonstrate a real effectiveness
against some skin disorders. Vitamins and minerals play an
important role in skin health and some of them are used to
treat some skin disorders, as for instance vitamins B9 and
B12, in combination, against vitiligo or zinc and acne.
Milk is also a source of proteins and peptides. Indeed; some
milks peptides are able to attenuate stress, which is one
of the risk factors of skin disorders. Then, lactoferrin and
alpha-lactalbumin demonstrated a certain efficiency against
Herpes simplex virus-1 and -2 and cutaneous papilloma
virus respectively. In addition to anti-viral and anti-fungal

actions, the milk peptides and proteins have anti-microbial


action, as for instance lactoferrin. Another important
application is the relief of the psoriasis symptoms with a
whey protein fraction enriched with growth factors. The
last application presented is the wound healing action of
mitogenic bovine whey extract on people suffering from
chronic leg ulcers.
The second macronutrient presented was the milk
phospholipids. At this moment, only one study showed the
interest of milk phospholipids for different health
applications. But, as for proteins and peptides, there could
be many beneficial effects to be identified for skin disorders.

Main references
Kim JH, Desor D, Kim YT, Yoon WJ, Kim KS, Jun JS, Pyun KH, Shim I. Eur J Clin Nutr. 2007 Apr;61(4):536-41.
Markus CR, Olivier B, de Haan EH. Am J Clin Nutr. 2002 Jun;75(6):1051-6.
Markus CR, Olivier B, Panhuysen GE, Van Der Gugten J, Alles MS, Tuiten A, Westenberg HG, Fekkes D, Koppeschaar HF,
de Haan EE. Am J Clin Nutr. 2000 Jun;71(6):1536-44.
Merens W, Booij L, Markus R, Zitman FG, Onkenhout W, Van der Does AJ. Br J Nutr. 2005 Sep;94(3):415-22.
Messaoudi M, Lefranc-Millot C, Desor D, Demagny B, Bourdon L. Eur J Nutr. 2005 Mar;44(2):128-32.
Scrutton H, Carbonnier A, Cowen PJ, Harmer CJ. J Psychopharmacol. 2007 Jul;21(5):519-24.
Gustafsson L., Leijonhufvud I, Aronsson A, Mossberg AK, Svanborg C. N Engl J Med. 2004 Jun 24;350(26):2663-72.
Comment in: N Engl J Med. 2004 Jun 24;350(26):2639-42. N Engl J Med. 2004 Oct 14;351(16):1692-3; author reply 1692-3.
Drouin R, Moroni O, Cantin K, Juneau C. Altern Med Rev. 2008 Jun;13(2):145-52.
Drouin R, Lamiot E, Cantin K, Gauthier SF, Pouliot Y, Poubelle PE, Juneau C. Can J Physiol Pharmacol. 2007 Sep;85(9):943-51.
Poulin Y, Bissonnette R, Juneau C, Cantin K, Drouin R, Poubelle PE. J Cutan Med Surg. 2006 Sep-Oct;10(5):241-8.
Poulin Y, Pouliot Y, Lamiot E, Aattouri N, Gauthier SF. J Cutan Med Surg. 2005 Dec;9(6):271-5.
Varelias A, Cowin AJ, Adams D, Harries RH, Cooter RD, Belford DA, Fitridge RA, Rayner TE. Wound Repair Regen. 2006
Jan-Feb;14(1):28-37. Erratum in: Wound Repair Regen. 2007 Jan-Feb;15(1):163.

Previous issues
# 01 Proteins and Satiety
# 02 Alphalactalbumin and Human Nutrition
# 03 Proteins and Sport
# 04 Hydrolysates and Peptides
# 05 Dairy Calcium and Health
# 06 Magnesium and Potassium
# 07 Why are Sulfur amino acids so important?
# 08 Hyperprotein diet: are they useful or dangerous?
# 09 Evaluation of protein quality.
Overview of current and future methods
# 10 Special report from Congrilait 2002
The 26th World Dairy Congress
# 11 Lactoferrin: General review and
opportunities for the future
# 12 Bioactives components in milk
and their physiological function
# 13 Lactose intolerance : the medical point of view
# 14 Allergy: myths and realities
# 15 The soy saga: trying to understand the wave.

# 16 Whey protein and weight management,


satiety and muscle metabolism
# 17 Bone health; not just calcium
# 18 Protein metabolism in endurance

and strength athletes
# 19 To salt or not to salt?
# 20 The emerging role of whey protein

in antioxidant and glycaemic regulation
# 21 Whey Protein and caseinates:

Different Physiological Advantages

This journal is published by ARMOR PROTEINES


Director of publication: Bernard FROMAGE
Editor in chief: Simon LEVESQUE
Author: Maggy LEBORDAIS
Co-author: Takashi MIKOGAMI

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