ArticlePDF AvailableLiterature Review

The clinical benefit of moisturizers

Authors:
  • Eviderm Institute

Abstract and Figures

Moisturizing creams marketed to consumers often contain trendy ingredients and are accompanied by exciting names and attractive claims. Moisturizers are also an important part of the dermatologist's armamentarium to treat dry skin conditions and maintain healthy skin. The products can be regarded as cosmetics, but may also be regulated as medicinal products if they are marketed against dry skin diseases, such as atopic dermatitis and ichthyosis. When moisturizers are used on the so-called dry skin, many distinct disorders that manifest themselves with the generally recognized symptoms of dryness are treated. Dryness is not a single entity, but is characterized by differences in chemistry and morphology in the epidermis depending on the internal and external stressors of the skin. Patients and the society expect dermatologists and pharmacists to be able to recommend treatment for various dry skin conditions upon evidence-based medicine. Learning objective Upon completing this paper, the reader should be aware of different types of moisturizers and their major constituents. Furthermore, s/he will know more about the relief of dryness symptoms and the functional changes of the skin induced by moisturizers.
Content may be subject to copyright.
© 2005 European Academy of Dermatology and Venereology
1
CPD PAPER
JEADV
(2005)
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, 000–000
DOI: 10.1111/j.1468-3083.2005.01326.x
Blackwell Publishing, Ltd.
The clinical benefit of moisturizers
M Lodén*
ACO HUD AB, Stockholm, Sweden,
*
Corresponding author: ACO HUD AB, Box 622, SE-194 26 Upplands Väsby, Sweden, tel. +46 859002951;
fax +46 859002980; E-mail: marie.loden@acohud.se
ABSTRACT
Moisturizing creams marketed to consumers often contain trendy ingredients and are accompanied by
exciting names and attractive claims. Moisturizers are also an important part of the dermatologist’s arma-
mentarium to treat dry skin conditions and maintain healthy skin.
The products can be regarded as cosmetics, but may also be regulated as medicinal products if they are
marketed against dry skin diseases, such as atopic dermatitis and ichthyosis.
When moisturizers are used on the so-called dry skin, many distinct disorders that manifest themselves
with the generally recognized symptoms of dryness are treated. Dryness is not a single entity, but is charac-
terized by differences in chemistry and morphology in the epidermis depending on the internal and external
stressors of the skin. Patients and the society expect dermatologists and pharmacists to be able to recom-
mend treatment for various dry skin conditions upon evidence-based medicine.
Learning objective
Upon completing this paper, the reader should be aware of different types of moistur-
izers and their major constituents. Furthermore, s/he will know more about the relief of dryness symptoms
and the functional changes of the skin induced by moisturizers.
Key words:
botanicals, dryness, emulsifiers, humectants, inflammatory disorders, lipids, skin permeability
Received: 29 August 2004, accepted 29 November 2004
Introduction
The desire to apply oily materials to the skin is almost
instinctive and may be as old as mankind itself. Moisturizers are
also the most prescribed products in dermatology. Treatment
with moisturizers aims at maintaining skin integrity and the
well-being by providing a healthy appearance of the individual.
The skin forms a perceptual interface for the organism and is
a critical structural boundary. The structure, composition,
formation and function of the stratum corneum (SC) have been
the subject of intense research over the last decades and its
integrity may be compromised as a result of both under- or over-
hydration. Abnormalities within the SC may be the primary
exacerbant of inflammatory skin diseases.
1
The types of problems covered by the term dry skin may not
always be diminished by an increase in skin hydration. Moistur-
izers are therefore adapted to perform many roles on the skin
surface. The structure and function of moisturizers are sur-
prisingly sophisticated, and many are equidistant between
cosmetics and drugs. The chemistry and function of dry skin and
moisturizers is a challenging subject for the practicing derma-
tologist, as well as for the development scientist within the
pharmaceutical and cosmetic industry (fig. 1).
2
Many healthcare professionals and patients overlook the
importance of moisturizers in maintaining an intact and
healthy skin and do not consider them to be ‘active treatments.
Compliance is a great challenge faced in the management of
skin diseases. If the moisturizers are used in too small quantities
they will have limited value.
3
The healthcare provider’s role
should emphasize continuity of care, patient satisfaction and
fig. 1 The quality and function of the cream will influence the quality and
function of the skin and thereby the well-being of the treated individual.
2
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product selection – all vital to protecting skin integrity and
enhancing the quality of life.
This paper will address some of the actives in moisturizers
and provide the reader with more insight into the mechanism
and evidence behind their effect.
What is a moisturizer?
Treatment of the skin can be performed with stay-on products,
such as ointments, creams, lotions, oils and gels. During
cleansing, oils can also be conveniently deposited on the skin by
the use of bath additives or by the use of cleansing products,
which leave an oily film after their removal.
4–6
The term ‘emollient’ implies (from the Latin derivation)
a material designed to soften the skin, i.e. a material that
smooths’ the surface to the touch and makes the surface look
smoother to the eye. The term ‘moisturizer’ is often used syn-
onymously with emollient. The term implies the addition of
water to the skin and therefore humectants are often included
in moisturizers to increase the water-binding capacity of the SC.
In the
International Cosmetic Ingredient Dictionary
, approxi-
mately 125 substances are listed as humectants and almost 200
hygroscopic materials are used to increase the water content of
the skin.
7
Irrespective of whether a cream contains humectants
or not, the term moisturizer is used in this paper to discuss various
types of formulations and their influence on the skin.
Formulation terminology and macroscopic
characteristics
Knowledge about the interplay between ingredients in
moisturizers is fundamental to get a stable and cosmetically
attractive product with preferred impact on the skin.
Greasiness, stickiness and the smell of some products can be
difficult to accept.
Creams are the most common types of delivery system used
for moisturizers. In its simplest form, creams are a two-phase
system (emulsion) containing two immiscible liquids – oil and
water, one of which is dispersed in the other in the form of
microscopic or submicroscopic droplets. Usually the outer
phase is larger than the inner phase. The ratio between oil and
water is important, as well as the type of oil and the amount and
type of other ingredients. The droplet size is often between 1
µ
m
and 100
µ
m, which gives white formulations. Emulsifiers pro-
vide stability by collecting at the interface of the two phases and
embed the droplets. Emulsifiers combine both hydrophilic and
lipophilic components in one molecule and turn their nonpolar
hydrocarbon end into the oil phase and their polar end into the
water phase.
Oil-in-water (O/W) emulsions are more common than
water-in-oil (W/O). In O/W emulsions, the oil content varies
between 15% and 30%, although other levels can be found.
With increasing oil content the greasiness of the formulation
may increase. With the introduction of new types of emulsifiers
it possible to achieve lower oil content also in W/O emulsions,
which improves their cosmetic properties. The outer phase has
a major impact on the cosmetic properties of the formulation.
Oils in the outer phase make the formulation more resistant to
wash-off, whereas if the oil is dispersed in the water phase, the
emulsifiers will facilitate re-emulsification upon exposure to
water.
Ointments are a single-phase system, where hydrophilic
ointments are preparations that are miscible with water in con-
trast to hydrophobic ointments that are not miscible with water.
When large amounts of finely dispersed solids are incorporated
in ointments, they are called pastes (e.g. zinc pastes). Gels are
hydrophilic or hydrophobic liquids that are gelled by means of
suitable gelling agents. Liquids could be solutions, suspensions
or emulsions. Bath oils are usually semitransparent hydropho-
bic solutions that may adhere to the skin upon contact. Lotions
are usually emulsions with lower viscosity and lower content of
oils than creams.
Topical formulation terminology does not always have a dis-
tinct definition of the words oils, fats and lipids. These words
are often interchangeable, as in the present review. The group
of substances may be defined in terms of solubility in organic
solvents and that they should provide a greasy feeling. Oils
and fats are known as oils or fats depending on whether they
are liquid or solid at room temperature. The substances are
mainly mixtures of triglycerides bulk storage material produced
by plants and animals. The chemical structure of triglycerides
consists of a glycerol fragment, esterified with three fatty
acids. Mineral oils and silicon oils are other types of semisolid
materials with oily properties. Mineral oils are hydrocarbons
derived from petroleum and silicons originate from silica
found in sand, quartz and granites. The properties of silicons
are derived from their molecular structure in addition to the
characteristics of the organic group joined to the silica. Lipids
can be defined as substances biochemically or functionally
related to fatty acids. Emulsifiers can also be considered as lipids.
Skin lipids consist mainly of ceramides, cholesterol and fatty
acids.
Chemical considerations and biochemical linkages
Oils, emulsifiers and humectants influence the aesthetic pro-
perties of the moisturizer and the stability of the formulation.
During the development steps, the concentration of fats, as well
as the type of fats and the amount and type of emulsifiers,
humectants, preservatives, are considered, as well as the impact
of other excipients, such as chelating substances, antioxidants,
fragrances, and other agents found in emulsions (Table 1).
Also, pH has to be addressed. Most formulations have pH
between 3 and 8. A number of creams are stabilized by emulsifiers
or contain ingredients that require pH above 7 to become stable,
for example emulsions with stearic acid as primary emulsifier.
Clinical Benefit of Moisturizers
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Lipid materials in moisturizers
Common fats in moisturizers
are mono-, di- and triglycerides, waxes, long-chain esters, fatty
acids, lanolin and mineral oils. Vegetable-derived materials are
more popular than animal-derived materials, probably because
of their natural origin. There is a large variety of fatty acids
among the glycerides, with the saturated fatty stearic acid, the
monounsaturated oleic acid and the polyunsaturated linoleic
acid being the most abundant fatty acids. The fatty acid profile
is typical for a certain oil and it determines to a great extent its
characteristics with respect to stability, skin feel and effects on
the skin. The most important feature of a fatty acid is the
number and distribution of double bonds over the carbon
chain. The degree of unsaturation influences the ease of
handling and those with a higher degree of unsaturation are
more easily oxidized. Oxidation is increased by the presence of
heat, light, metals and oxygen.
Oils from certain vegetables and fish contain essential fatty
acids (EFA). Fatty acids with the first double bond at the 6th
carbon atom counting from the end of the carbon tail is called
omega-6, whereas those with the first double bond at the
3rd carbon atom are called omega-3 fatty acids. Omega-6 and
omega-3 fatty acids are derived from linoleic and
α
-linoleic
acids, respectively. The essential fatty acids influence skin physio-
logy via their effects on skin barrier function, eicosanoid
production, membrane fluidity and cell signalling.
8
EFAs are
found predominantly within the epidermal phospholipids,
but are also incorporated in ceramides where they play a critical
role in barrier function. The most abundant EFA in the skin is
linoleic acid and its metabolite, arachidonic acid.
Polyunsaturated fatty acids in oils have been suggested to be
transformed enzymatically by the epidermis into ‘putative’ anti-
inflammatory products.
9
It has also been shown that small
hydrophobic compounds such as free fatty acids and cer-
tain oxysterols are recognized by nuclear hormone receptors,
the largest family of transcription factors. Oxidation of
long-chain fatty acids has been linked to the activity of peroxisome-
proliferating activated receptor (PPAR
α
).
10
Cutaneous inflam-
mation as it occurs in irritant contact dermatitis is reduced by
the PPAR
α
-agonist linoleic acid in mice.
11
Moreover, ac tivator s of
liver X receptors display anti-inflammatory activity in both
irritant and allergic models of dermatitis.
12
Canola oil and
its unsaponifiable enriched fraction have also been found to
reduce surfactant-induced irritation in humans, whereas other
lipids (e.g. petrolatum, fish oil, borage oil) did not differ from
the water control.
13
Studies have also demonstrated that activa-
tors of liver X receptors stimulate epidermal differentiation
and improve permeability homeostasis during fetal rat skin
development.
14
Evening primrose oil (
Oenothera biennis
or
Oenothera lamar-
kiana
) and borage oil (
Borago officinalis
) have gamma-linoleic
acid (GLA) levels over 9% and 20%, respectively. A range of die-
tary oil supplements has been suggested effective for treatment
of atopic dermatitis and some studies have also shown promis-
ing effects of evening primrose oil when administered orally to
atopic patients.
15
However, this has not been confirmed in more
recent double-blind and placebo-controlled studies, neither on
adult patients
16,17
nor on children.
18
Seafood is known to contain omega-3 fatty acids like eico-
sapentaenoic (EPA), docosahexaenoic and stearidonic acid.
Clinical studies also suggest that oral or topical supplements
of EPA and/or omega-3 derivatives decreases the severity of
psoriasis.
19,20
However, oral treatment and topical treatment
in randomized and double-blind studies could not support
the effect on moderate psoriasis.
21,22
Topical treatment with
sunflower seed oil (rich in linoleic acid) increased the level of
linoleic acid of the epidermal phospholipids, but did not improve
the disease or change transepidermal water loss (TEWL).
23
Waxes may be classified into animal, vegetable and mineral
type. The most commonly used animal wax is lanolin. Lanolin
(from the Latin
lana
for wool and
oleum
for oil) is secreted by
the sebaceous glands of the sheep. Unlike human sebum, lano-
lin contains no triglycerides, but contains a complex mixture of
esters, disesters and hydroxy esters of high molecular weight
lanolin alcohols and lanolin acids. Beeswax is a complicated
mixture of hydrocarbons, esters and fatty acids. A typical exam-
ple of a vegetable-derived wax is carnauba, which is obtained
from the leaves of the carnauba palm tree.
Mineral oils are derived from petroleum. The two most
important materials are liquid paraffin (also called mineral
oil and paraffinum liquidum) and petrolatum, consisting of
complex combinations of hydrocarbons. Depending on the
distribution of the molecular weight, materials with different
viscosity are obtained. During the refining process, the hydro-
carbon material is hydrogenated to create oxidation-resistant
molecules throughout, from the liquid to the solid waxes. This
gives a long shelf life to the products. Petrolatum has been used
in topical formulations since its discovery by Chesebrough in
1872.
24
Emulsifiers
The emulsifiers can be ionic or non-ionic. The ionic
types are either anionic or cationic, depending on the surface-
active portion of the compound. Long-chain fatty acids are one
group of frequently used anionic emulsifiers, for example stearic
acid and palmitic acid, also found in the skin barrier lipids,
Table 1 Ingredients in emulsions and typical levels in percent
Essentials for stability Water (80)
Oils (20)
Emulsifiers (5)
Preservatives (0.5)
Others for possible enhancement of
biological or emotional effect, or
stability
Humectants (5)
Silicones (1)
Herbal extracts (2)
Fragrance (0.2)
Antioxidants and chelators (0.5)
4
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(fig. 2). The acids are often partially neutralized with cationic
excipients in the preparation of the cream. The concentration
ranges from approximately 1–10%. Fatty acids with a chain
length of 14–22 carbons are also found in the epidermal tissue.
Cholesterol is another component of the lipid bilayer, which is
also found as an emulsifier (non-ionic) in moisturizers.
Non-ionic emulsifiers depend primarily upon hydroxyl groups
and ether linkages (from polyhydric alcohol anhydrides and
polyoxyethylene chains) to create the hydrophilic action.
The effects of emulsifiers on skin barrier properties are not
well described, but non-ionic emulsifiers are expected to be less
irritating than ionics, although non-ionics also interact with the
skin barrier function.
25
Application of structural lipids from SC
has been suggested to be more efficient than other type of lipids
to correct hydration and scaling disorders.
26,27
Furthermore, it has been shown that the complete mixtures
of ceramide, fatty acid and cholesterol, or pure cholesterol
allowed normal barrier recovery in barrier-abrogated murine
skin, whereas two-component mixtures of fatty acid plus
ceramide, cholesterol plus fatty acid or cholesterol plus
ceramide-delayed barrier recovery.
27
Hydrating substances
The majority of humectants used in
moisturizers are low molecular weight substances with water-
attracting properties. A few high molecular weight substances
are also used, e.g. polymers such as hyaluronic acid. Humectants
differ in water-binding capacity as well as in ability to penetrate
and influence the degree of skin hydration.
Glycerol is probably the most commonly used humectant.
The Swedish scientist, C.W. Scheele discovered that glycerol
could already be made by hydrolysis of olive oil in 1779. Glycerol
has been suggested to ameliorate dry flaky skin by facilitating
the digestion of the superficial desmosomes in subjects with dry
skin.
28
Glycerol also modulates the phase behaviour of SC lipids
in vitro
and prevents crystallization of their lamellar structures
at low relative humidity.
29
In dry skin the proportion of lipids
in the solid state may be increased, and glycerol may then help
to maintain the lipids in a liquid crystalline state at low relative
humidity.
29,30
In sebaceous gland-deficient mice, dryness has been found
linked to reduced levels of glycerol because of the primary
source for glycerol: triglycerides.
31
This type of dryness may also
be applicable to clinical situations where sebaceous glands are
absent or involuted, such as in prepubertal children showing
eczematous patches that disappear with the onset of sebaceous
gland activity. Moreover, xerosis in the distal extremities of aged
skin and patients receiving systemic isotretinoin for treatment
of acne has been suggested to be linked to glycerol depletion
because of lower sebaceous gland activity.
31
Propylene glycol and butylene glycol are other frequently
used alcohols with humectant properties. Propylene glycol
often is often used as a solvent and vehicle for substances un-
stable or insoluble in water and is regarded as a penetration
enhancer.
Panthenol is another alcohol that is converted in tissues to
D-pantothenic acid (vitamin B
5
), a component of coenzyme A
in the body. The substance can be isolated from various living
creatures, which gave the reason for its name (panthoten is
Greek for everywhere).
32
Panthenol is found in topical treatments
for rhinitis, conjunctivitis, sunburn and for wound healing
(ulcers, burns, bed sores and excoriations).
32,33
Topically applied
panthenol is reported to penetrate the skin and hairs and to be
transformed into panthothenic acid.
32,34
PCA is the cosmetic ingredient term used for the cyclic
organic compound known as 2-pyrrolidone-5-carboxylic acid
(also pidolic acid). The sodium salt is a naturally occurring
humectant in the SC corresponding to approximately 2% by
weight in the SC.
35
PCA belongs to a fraction of low molecular
humectants, which is termed ‘natural moisturizing factor’
(NMF).
36
Treatment of solvent-damaged guinea pig footpad
corneum with humectant solutions shows that the water held
by the corneum decreases in the following order: sodium PCA
> sodium lactate > glycerol > sorbitol.
37
Another important group of humectants is the
α
-hydroxy
acids (AHA). AHA is an organic carboxylic acid in which there
is a hydroxy group at the two, or alpha (
α
), position of the car-
bon chain. Formulations containing an AHA have an acidic pH
in the absence of any inorganic alkali or organic base. Lactic,
glycolic and tartaric acids belong to AHA. Lactic acid is a part
of NMF and has been used in topical preparations for several
decades because of its buffering properties and water-binding
capacity.
37
The concentrations used for treatment of dry skin
disorders have ranged up to 12%.
38
Urea is another physiological NMF. Solutions containing
20% urea has been proposed to reduce experimentally induced
itching.
39
Urea is used as a 10% cream for the treatment of
fig. 2 Similar types of lipids are embedding the oi
l
droplets in emulsions as are embedding the cor
-
neocytes in the stratum corneum.
Clinical Benefit of Moisturizers
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ichthyosis and hyperkeratotic skin disorders,
24,40
and in lower
concentrations for the treatment of less severe dryness.
Botanical substances
A number of herbal products and extracts
have been used in topical formulations since historical times
and are part of dermatology practice.
41
Herbs are identified in
Latin by their Linnaean description, where every entity is given
two names. This binominal system was introduced by the
Swedish naturalist Carl Linnaeus in the 18th century. The
rationale for the inclusion of herbal extracts in moisturizers
may not always be based on controlled studies or evidence-
based meta-analyses of clinical trials.
41
Instead herbal extracts
may be added for marketing reasons to nurture consumer
interest in the perceived benefits of ‘natural ingredients’ on the
skin. Furthermore, there are many pitfalls in using herbs.
The right species must be chosen, the time of harvest, the
method of preparation and the stability of the actives have to
be determined, making it hard to judge the quality of the
treatment.
Perhaps no other natural ingredient is more widely found in
moisturizers than aloe. There are more than 300 species of
Aloe
plants, where aloe vera is now referred to by taxonomists as
Aloe
barbadensis
.
42
The different species of
Aloe
have different chem-
ical compositions and many investigations of the constituents
found do not report the species studied.
42
Much of the con-
sumer perception about the efficacy of Aloe is anecdotal.
Healing of burns and skin ulcers, along with antibacterial
and anti-inflammatory properties are proposed effects, but
evidence to support its use is not compelling.
42
Several studies
of the efficacy of aloe vera components have shown conflicting
results and clinical investigations that incorporate vehicle
controls are considered necessary.
42
Oatmeal baths for soothing rashes have been part of nursing
practice for decades.
41
Oatmeal is processed oats (
Ave nao sativa
)
.
Allantoin is the synthesized active from the comfrey root
(
Symphytum officinale
), known as aluminium dihydroxy allan-
toinate. It is frequently marketed in moisturizers for the healing
of dry skin and is also suggested to be a keratolytic agent. Con-
trolled studies confirming the efficacy are lacking.
Plant-derived polyphenols, sometimes called bioflavonides,
are becoming increasingly popular in topical products because
of their antioxidant properties. Normal skin contains several
antioxidants, such as ascorbic acid, vitamin E, ubiquinol and
uric acid. During oxidative stress, the levels of these substances
in the skin are affected and topical treatment with antioxidants
may therefore be beneficial to the skin. For example, red tomato
(
Lycopersicum esculentum
) contains an unsaturated, open-chain
carotenoid with protective effect against UV-radiation.
43
Preservatives, antioxidants and chelators
Preservatives are
included in formulations to kill or inhibit the growth of
microorganisms inadvertently introduced during use or
manufacturing. Contaminating organisms may be either
pathogens or nonpathogens. The ideal preservative must have a
broad spectrum of activity; it must be safe to use; it should be
stable in the product and it should not affect the physical
properties of the product. No single preservative meets all these
requirements and usually a combination of substances is used.
Phenoxyethanol and parabens (methyl-, propyl-, ethyl- and
butylparaben) belong to the most frequently used preservatives
in moisturizers.
The efficacy of the preservative system is also influenced by
pH and other ingredients in the formulation. Certain sub-
stances, such as ethanol and propylene glycol, may enhance the
effect of the preservatives. In addition, alcohols may, on their
own, prevent contamination of the product when they are used
at high concentrations.
24
Antioxidants inhibit oxidation of ingredients by reacting
with free radicals and blocking the chain reaction. Typical anti-
oxidants are tocopherols (vitamin E), butylated hydroxytoluene
(BHT) and alkyl gallates.
24
Reducing agents, such as ascorbic
acid, may also act by reacting with free radicals, as well as
oxidize more readily than the ingredients they are intended to
protect.
Citric acid, tartaric acid and ethylenediaminetetracetic acid
(EDTA) and its salts have limited antioxidant activity them-
selves, but enhance the efficacy of antioxidants by reacting with
heavy-metal ions. Such substance is called chelating agents. The
chelated form has few of the properties of the free ion and for
this reason chelating agents are often described as ‘removing’
ions from solution.
24
The stability of the metal-edetate complex
depends on the metal ion involved and also on the pH. The
calcium chelate is relatively weak and EDTA will preferentially
chelate heavy metals, such as iron, copper and lead.
24
Whether it is preservatives, antioxidants or metal chelators that
may influence the SC remains to be elucidated. Divalent ions
such as calcium regulate the dissociation and chelating agents, such
as EDTA have been noticed to increase the rate of cell dissociation
ex vivo
.
44
Mixtures of magnesium and calcium salts have been
found to accelerate the barrier recovery in tape-stripped mice.
45
Characteristics of dry skin
Moisturizers are used on many distinct diseases that manifest
themselves with the generally recognized symptoms of dryness.
The dry-skin disorders are induced by complex interactions
between environmental and individual factors, Table 2.
46– 62
Table 2 Examples of factors contributing to dryness and eczema
Low environmental temperature, low humidity46,47
Exposure to chemicals, microorganisms48,49
Ageing and psychological stress50,51
Atopic eczema52–55
Psoriasis56,57
Ichthyosis58–62
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The impression of dryness is formed by inherent sensory
components in the skin, along with visible and tactile changes
of the surface.
63,64
A feeling of dryness, an uncomfortable skin
that is tight, painful, itchy, stings and tingles are symptoms
belonging to the affected person (Table 3).
The appearance of the skin is essential for the individual,
and a flawed presentation often results in reduced esteem by
self and others.
65
Visible changes include redness, a lacklustre
surface, dry white patches, flakes, cracks and even fissures.
The skin can also feel rough and uneven on touch (Table 2).
The severity and the extent of the dryness can be quantified
using various grading scales.
66
Clinical and patient judgement
of the disease may not always correlate, which may explain
discrepancies between clinical judgement and quality of life in
individual patients.
67
Besides cracks, dry skin may also have invisible barrier
defects, which can be measured as an increased TEWL.
Therefore, measurement of TEWL can be used to monitor
the kinetics in the repair of a deteriorated barrier function.
However, the permeability to water may not necessarily reflect
the permeability to other substances. Therefore, skin barrier
function is also assessed by evaluation of the skin reaction
following application of a biologically active substance.
68
Hydrating substances in the stratum corneum
Water in the SC is associated with the hydrophilic parts of
the intercellular lipids and with the keratin fibers in the
corneocytes.
69,70
Three types of water with different molecular
mobilities can be found in the SC. At a water content below
10%, the primary water is tightly bound, presumably to the
polar sites of the proteins.
69,71,72
NMF in the corneocytes accounts for 15–20% of the total
weight of the SC.
35,36
The main constituents are amino acids,
lactate, PCA and urea.
36
The elasticity and ability of the SC to
bind water decreases if NMF is extracted from the skin.
35,37,73–75
In skin diseases such as ichthyosis vulgaris
76,77
and psoriasis,
78
there is a virtual absence of NMF.
The epidermal protein, filaggrin is the precursor of the free
amino acids, urocanic acid and PCA belonging to NMF. In
ichthyosis vulgaris the stratum granulosum is thin or missing as
a result of a defect in the processing of profilaggrin, which also
is noticed as tiny and crumbly keratohyalin granules.
79
Activa-
tion of filaggrin proteolysis depends on the external water activ-
ity and can be blocked by maintaining a 100% humidity
atmosphere around the SC. In isolated SC
in vitro
, filaggrin pro-
teolysis takes place only between 80% and 95% relative humid-
ity, both higher and lower relative humidity block the
proteolysis. Therefore the SC has the ability to respond to
changes in external humidity by converting its reserves of filag-
grin into NMF. Under humid conditions, water-binding com-
ponents will be produced only in the most superficial SC, or
even not produced at all.
80
Evidence-based use of moisturizers
Different types of evidence can be ranked in term of importance
when decisions about clinical interventions are made (fig. 3).
81
The confidence from randomized controlled studies gives
stronger evidence for treatment effects than open studies.
Anecdotal evidence is provided by case reports, which are used
to alert health professionals to rare occurrences. Systematic
pooling of the results from similar trials increases the statistical
power of treatment effects. Such meta-analyses can change
weak evidence into stronger ones. Moreover, apparently con-
flicting results between studies may be compatible when a
statistical meta-analysis of the data has been performed. The
relevance of the data has to be judged, bearing in mind that
statistical significance is not the same as clinical significance.
Influence of moisturizers
Application of moisturizers to the skin induces tactile and
visual changes of the surface. The combination of substances
influences the initial feel of the product, its spreading behaviour
on the skin, whether it is absorbed and how fast and how
the skin looks and functions after its use. Immediately after
application of moisturizers, the water content in the SC is
Table 3 Commonly found characteristics of dry skin
Method Results
Visual Redness, a lackluster surface, dry white patches, flaky
appearance and even fissures
Sensory Feels dry, uncomfortable, painful, itchy, stings and tingles
Tactile Rough and uneven
Chemical Reduced water content and level of natural moisturizing factor.
Changed lipid composition
Functional Increased permeability, i.e. higher level of transepidermal
water loss and less resistance to absorption of noxious
substances
fig. 3 Certainty is increased by collecting and developing information in a
systematic way.81
Clinical Benefit of Moisturizers
7
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JEADV
(2005)
19
, 000–000
increased
82
and a smoothing of the surface can be observed, as
a result of the filling of spaces between partially desquamated
skin flakes.83,84 Thereafter, skin mechanics are changed85 and
the increased hydration will facilitate degradation of desmosomes
keeping the corneocytes together.28,44,86,87 A possible strengthening
of a weakened skin barrier function may also occur, which can
make skin less susceptible to attacks from noxious substances
and prevent the development of eczema.88–90 This may explain
why moisturizers are useful treatment adjuncts in inflammatory
dermatoses as steroid-sparing therapy.1,91 Acute and chronic
perturbations of barrier function may lead to epidermal
hyperplasia92,93 and cutaneous inflammation by increased
production and secretion of cytokines.94
Improvement induced by humectants
The benefit of using AHA in the treatment of dry and scaly skin
was observed already 30 years ago in patients with ichthyosis.95
More than 60 test materials, including a number of AHAs, were
incorporated into a hydrophilic ointment (acids at 5%) or plain
petrolatum, and applied twice daily to the selected test site
for 2 weeks. AHAs and closely related compounds were the
most effective, causing disappearance of scales from lesions or
restoring the skin to normal look.95 Improvement in dryness by
the inclusion of humectants has also been shown in some
vehicle-controlled studies on dry and irritated skin.62,96–102
In studies on patients, one might expect an improvement in
the impaired skin barrier function in association with improvement
of the clinical signs of dryness. However, clinical improvement
of dryness signs does not necessarily induce normalization of
TEWL. Ammonium lactate (12%) had no effect on TEWL,
despite clinical improvement of atopic dry skin.103 Furthermore,
deterioration of the barrier function can be induced by the
treatment. A moisturizer with 5% lactic acid and 20% propylene
glycol actually increased TEWL in ichthyotic skin.61 The same
results was also found in xerotic legs treated with 15% glycolic
acid.104 The xerotic legs showed less xerosis, but TEWL increased
as did the susceptibility to externally applied substances.104
However, one moisturizer with 10% urea reduced TEWL in
ichthyotic patients62 and 5% reduced TEWL in atopic pati-
ents105 and made skin less susceptible against irritation to
sodium lauryl sulphate (SLS).89 A urea moisturizer was also
superior to a glycerol moisturizer in lowering TEWL in a double-
blind study on atopic patients.106 TEWL was also reduced in dry
skin by treatment with moisturizers containing urea.107
In sodium lauryl-sulphate-induced irritated skin, panthenol
has been found to promote skin barrier repair and SC
hydration.108 Moreover, skin redness decreased more rapidly by
panthenol treatment.108 Also, the humectant glycerol has been
found to stimulate barrier repair in SLS-damaged human
skin.109
Skin surface pH has also been suggested to influence barrier
recovery. The initiation of the recovery was delayed when
severely damaged mice skin was exposed to neutral or alkaline
pH, whereas the skin recovered normally during exposure to
solutions buffered to an acidic pH.110 The delay in barrier
recovery was suggested to be a consequence of inhibition of
barrier lipid formation.110 However, in surfactant-damaged
human skin, no difference in recovery was observed between
treatment with a cream with either pH 4 or 7.111
In addition, pH may affect the desmosomes keeping the cor-
neocytes together.44,86,87 In excised skin, the rate of spontaneous
cell dissociation is highest at neutral to weakly alkaline pH and
decreases at lower pH.44
Improvements induced by lipids
Application of lipids to the skin surface produces skin hydration
by several mechanisms. The most conventional is occlusion,
which implies a simple reduction of the loss of water from
the outside of the skin. Common occlusive substances in
moisturizers are lipids, for instance petrolatum, beeswax,
lanolin and various oils.112
These lipids have long been considered to exert their effects
on the skin solely by forming an inert layer on the skin. How-
ever, topically applied lipids penetrate the skin19,113–117 and
application of structural lipids from SC has been suggested to be
more efficient than other type of lipids to correct hydration and
scaling disorders.26,27 Topically applied lipids have also been
suggested to be able to influence the cutaneous inflammation
because of a possible anti-inflammatory action.
Studies using experimental models of dryness Topically applied
products usually accelerate normalization of the skin in experi-
mentally damaged skin.27,109,118–120 Petrolatum is absorbed into
delipidized skin and speeds up the barrier recovery to water.121
A commercially available physiological lipid mixture was also
found to promote barrier recovery, in comparison to the
untreated control area in SLS-irritated and tape-stripped
human skin.120 However, the barrier recovery was not superior
to petrolatum (placebo).120,122 Commercially available
moisturizers have also been found to reduce elevated TEWL in
acetone-treated mice skin compared to untreated areas during
a 24-h test period.123
It has been suggested that the ratios of physiological lipids are
important,124 as physiological lipids have been shown to pene-
trate deeper into the skin and either promote or delay recovery
depending on composition.27 Another hypothesis is that the
percentage of lipids in the formulation determines the efficacy,
as a relationship between the rate of recovery of experimentally
damaged skin and the level of lipids has been observed.118
Another interesting aspect is that not only lipids but also non-
ionic emulsifiers may reduce TEWL in irritated skin.25
Hence, suggestions how to tailor moisturizers for various
skin abnormalities have been proposed.27,118,124–126 It is impor-
tant to support the results from experimental studies by data
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© 2005 European Academy of Dermatology and Venereology JEADV (2005) 19, 000–000
from the target patient group, where the time course for the
effect ideally also should be considered.
Studies in patients In an uncontrolled study of infantile sebor-
rheic dermatitis, topical treatment with borage oil was shown
to improve the skin condition and normalize TEWL.116,127
Moreover, a physiological lipid mixture decreased TEWL and
improved atopic dermatitis in an open study in children.128
However, in patients with damaged skin as a result of wet
work, a moisturizer without humectant did not change TEWL
despite clinical improvement.129 Neither did petrolatum and
hydrophilic ointment change TEWL in six patients with atopic
xerosis.130
Placebo-controlled studies of the influence of different lipid
compositions on dry skin disorders are rarely found in the
scientific literature. This may be the result of difficulties in
defining an appropriate control treatment, or that no signi-
ficant differences have been found making the study of less scien-
tific interest. Formulations without any humectants are more
often used as controls when the efficacy of the humectants is
evaluated. In such studies, the control treatment usually show a
favourable effect on the skin disorder.62,96–102
Treatment of normal skin and the prevention of
dryness
Moisturizers are recommended for use in normal skin to
prevent the appearance of dryness.131,132 Despite their wide-
spread use, only a few studies have focused on their influence on
the permeability barrier. Treatment with moisturizers may well
influence the barrier properties of normal skin. Treatments
usually increase skin hydration, but no increase in TEWL tends
to follow.88,133,134 However, changes in skin reactivity have been
noted. A lipid-rich cream without any humectant had no
influence on TEWL, but skin susceptibility to SLS-irritation was
increased compared to untreated skin.133 Increased skin
reactivity was also found in a long-term study using benzyl
nicotinate as a marker for permeability, where the time to
maximum response was shorter for the cream-treated area
compared to the untreated.135 In addition, the time to induce
vasodilatation was shorter for the lipid-rich cream than for
a moisturizer containing 5% urea.135 Increased sensitivity to
nickel was also found when nickel-sensitive humans treated
their skin with moisturizers without humectant, compared to
treatment with moisturizer with humectant.136
On the other hand, areas treated with the glycerol-containing
cream showed less reactivity to nickel than those treated with a
cream without any humectant.136 Furthermore, repeated appli-
cations of urea-containing moisturizers have been found to
reduce TEWL and make skin less susceptible to SLS-induced
irritation.88,107,119 An increased resistance to SLS-induced
irritation and xerosis has also been found after treatment with
AHA.137,138 Lactic acid has been suggested to stimulate the
production of ceramides.138 Moreover, another humectant,
dexpanthenol, has been reported to decrease TEWL after 7 days
treatment.139
Adverse effects
Compared to traditional drugs used by dermatologists,
moisturizers are rarely associated with health hazards, although
they may be used on large body areas over a large part of the
human life span. Strictly certified purification of tallow from
animals eliminates any risk associated with the bovine spongiform
encephalopathy (BSE). Vegetable oils are usually also highly
purified in order to remove impurities, such as proteins in peanut
oil, which can elicit sensitization reactions in allergic individuals.140
However, intoxication has occurred. For example, topical
treatment with salicylic acid in children with lamellar ichthyosis141
and treatment with high concentrations of propylene glycol in
burn patients have resulted in poisoning.142 Moreover, some
products, particularly Chinese herbal creams have been shown
repeatedly to be adulterated with corticosteroids, which may
cause serious side effects.143
Various forms of skin discomfort from topical preparations
are more common encountered, as virtually any substance can
cause skin reactions in sensitive areas in some individuals.
Atopics are particularly at risk for adverse skin reactions
because of the impaired barrier function. Facial skin is also
more sensitive than other body regions,144,145 possibly the result
of a less efficient barrier with smaller number of SC cell layers
and the presence of large follicular pores.146
Visible and invisible irritation
The most common adverse reactions to moisturizers are
sensory reactions or subjective sensations (no signs of inflam-
mation) immediately after application. Smarting, burning and
stinging sensations are examples of such reactions among users
of moisturizers. Humectants, such as lactic acid,147 urea145,148
and PCA,149 and preservatives like benzoic acid149 and sorbic
acid145 are known to cause subjective sensations. The alcohol
propylene glycol may also cause adverse skin reactions in
normal subjects at concentrations as low as 2% in dermatitis
patients.150 The nature of the skin response has been classified
into four mechanisms: (a) subjective or sensory irritation, (b)
allergic contact dermatitis, (c) non-immunologic contact
urticaria and (d) irritant contact dermatitis.147,151
When atopics are asked to judge the degree of adverse skin
reactions to urea-containing moisturizers, 20– 40% report
smarting sensations (a sharp, local, superficial effect similar to
the reaction noted to acidic solutions).152 Combinations with
corticosteroids do not eliminate stinging and 12–30% of
patients using hydrocortisone creams with 4–20% urea on
eczema also reports stinging.98,153,154 The humectant glycerol
appears to be very well tolerated.100
Clinical Benefit of Moisturizers 9
© 2005 European Academy of Dermatology and Venereology JEADV (2005) 19, 000–000
Moisturizers are usually free from strong irritants, but
repeated exposure of sensitive areas to mildly irritating prepa-
rations may cause dermatitis. Strong irritants are usually easy to
identify, whereas weak irritants are less obvious to avoid. The
difficulties in avoiding weak irritants may contribute to a higher
frequency of chronic contact dermatitis than the acute form.155
For example, frequent immersion of the skin in water coun-
terproductive as far as the moisturization is concerned.156,157 In
addition, a classic hydrophilic ointment contains the well-
known irritant sodium lauryl sulphate as coemulsifier.24 Aque-
ous solutions of 1% sodium lauryl sulphate are commonly used
in experimental dermatology to induce irritation.158 Also, fatty
acids sometimes found in moisturizers as emulsifiers can influ-
ence skin barrier properties.25,159 Non-ionic emulsifiers are the
preferred stabilizers for emulsions because of their mildness,
but TEWL measurements indicate that also some of them may
produce invisible barrier damage in normal skin.25 Further-
more, non-ionic polyethylene glycol emulsifiers are susceptible
to oxidation, inducing formation of peroxides and aldehydes
(e.g. formaldehyde).160
The use of mild soaps and shower/bath oils containing nox-
ious substances may also constitute a risk for adverse reactions.
Barrier-deteriorating substances from ‘mild’ soaps and shower
oils remained on the skin after rinsing.161,162 Repeated barrier
insults with subclinical skin damage will make the skin vulner-
able to further irritation and may lead to epidermal hyperplasia
and inflammation.1
It is not known whether sensory sensations following appli-
cations of moisturizers affect barrier properties of the skin, but
it has been shown that lactic acid stimulates the production of
ceramides and make skin more resistant to xerosis.138
Contact allergy
Fragrances and preservatives are identified as the major
sensitizers in topical formulations. Almost all moisturizers in
the supermarket contain fragrances and over 100 fragrance
ingredients have been identified as allergens.163 However, it
appears that fragrances may be used without introducing an
increased rate of skin reactions164,165 and the new European
cosmetic legislation facilitates for consumers to avoid fragrance
materials with known risks of sensitization.166
Humectants, emulsifiers and oils hardly ever cause contact
allergy.163 Lanolins are sometimes proposed to be a frequent
cause of contact allergy, but this is believed to be to the result of
inappropriate testing conditions leading to false-positive reac-
tions.163 Adverse reactions to herbal extracts are rare, probably
a manifestation of the trivial amounts present in the finished
product. However, virtually all herbal remedies can cause allergic
reactions and several can be responsible for photosensitization.143
For example, aloe vera, black cumin oil, chamomile, Chinese
herbal mixture, olive oil, tea tree oil and inula helenium, have
been reported to be able to cause allergic contact dermatitis.143
Dosages and compliance
Finding the most suitable moisturizer for an individual may be
a matter of trial and error (fig. 4). The cosmetic properties and
the simplicity to use the products are important parameters to
achieve the desired treatment effects. Low compliance can be a
problem and the process of treating the skin adds to the burden
of having the disease. The patients only allow a short time
for the treatment and practical problems discourage the sub-
jects from complying with a skin care program. Treatment
of children with atopic dry skin may also have an impact
on emotional development depending on the quality of the
interaction between the parent and child. Creaming may feel
soothing and comforting, punitive and intrusive, or func-
tional and neutral.167 Strong odour from ingredients, greasy
compositions and uncomfortable skin reactions are examples
of disagreeable features to the patients. Easily applied and
rapidly absorbed emulsions with immediate effect are more
likely to be perceived as beneficial by the user and their
continued use encouraged.
Dermatologists encourage patients prone to dermatitis to use
moisturizers also when the skin is under control131,132 and to
use bath oils, as they are considered to leave a protective oily
film on the surface and reduce xerosis.4–6 Similar to other
actives, the efficacy of moisturizers is likely to depend on the
dosage, where compliance is a great challenge faced in the man-
agement of skin diseases. Hence, in the case of topical treatment
it is often difficult to estimate the amount applied by the
patient. This makes it difficult to compare the effectiveness of
moisturizers and may also cause doubts about the compliance
with the prescribed treatment. Intensive education from a spe-
cialist dermatology nurse have resulted in 800% increase in the
use of moisturizers (to 426 g weekly of emollient cream/oint-
ment) and no overall increase in the use of topical steroids,
accounting for potency and quantity used.3 This resulted in
89% reduction in the severity of eczema.
Differences in dosing have been noted among self-application
vs. operator assisted application of creams.168 Self-application
fig. 4 Product claims, cosmetic properties and packaging will add to the
inherent biological response of moisturizers and increase compliance and
final effect.
10 Lodén
© 2005 European Academy of Dermatology and Venereology JEADV (2005) 19, 000–000
resulted in larger amount applied per unit area.168,169 The dis-
tribution of the cream has also been found to vary over the
treated region and the real surface.168 In addition, distribution
within the treated area differs depending on the type of
vehicle.170 A thick ointment with only a few percent of water was
equally distributed in the centre and periphery of the treated
area, whereas formulations with lower viscosity and more
volatile ingredients (e.g. creams) were less evenly spread on the
skin.170 Moreover, jars promoted use of larger quantities than
the same cream in a tube (1.7 vs. 0.7 mg/cm2, respectively).169
However, it may be expected that moisturizer treatment seldom
requires the same application rate on different sites because of
the various severities of the dryness in the treated areas.
Once applied to the skin, the ingredients can stay on the sur-
face, be absorbed into the skin, be metabolized or disappear
from the body by evaporation, sloughing off or by contact with
other materials. Only 50% of applied creams were found to
remain on the surface after 8 h.171 Transfer of the actives to
surrounding surfaces appears to be easier from creams and
ointments than from lotions and tinctures.172
Conclusions and outlook
Clear evidence exists that moisturizers are important in
the treatment of different dry skin conditions. Furthermore,
moisturizers prevent the appearance of dryness, and some
formulations may also improve skin barrier function and make
skin less prone to eczema.1 The key to future moisturizer
therapy will be to tailor the treatment to the distinct
abnormalities that manifest themselves with the generally
recognized symptoms of dryness. Ranking the efficacy will be
facilitated by an increased knowledge of their interaction with
the skin. So far, the links between the abnormality and the
composition of the moisturizer remain largely unexplored.
Therefore, it may be a matter of trial and error to find the most
suitable formulation for an individual. Today, the best product
for an individual may be the one they prefer because they will
use it regularly and it will therefore be effective. Pharmacists
could make a major contribution in this area by actively
encouraging moisturizer use.
References
1Elias PM, Wood LC, Feingold KR. Epidermal pathogenesis of
inflammatory dermatoses. Am J Contact Dermat 1999; 10: 119–
126.
2Lodén M, Maibach HI. Dry Skin and Moisturizers; Chemistry and
Function, 1st edn. CRC Press, Boca Raton, 2000.
3Cork MJ, Britton J, Butler L et al. Comparison of parent
knowledge, therapy utilization and severity of atopic eczema
before and after explanation and demonstration of topical
therapies by a specialist dermatology nurse. Br J Dermatol 2003;
149: 582–589.
4Hill S, Edwards C. A comparison of the effects of bath additives on
the barrier function of skin in normal volunteer subjects. J
Dermatolog Treat 2002; 13: 15–18.
5Stender IM, Blichmann C, Serup J. Effects of oil and water baths
on the hydration state of the epidermis. Clin Exp Dermatol 1990;
15: 206–209.
6Stanfield JW, Levy J, Ky riakopoulos AA et al. A new technique for
evaluating bath oil in the treatment of dry skin. Cutis 1981; 28:
458–460.
7Pepe RC, Wenninger JA. International Cosmetic Ingredient
Dictionary and Handbook. The Cosmetic, Toiletry, and Fragrance
Association, Washington, 2002.
8Rhodes LE. Essential fatty acids. In: Dry Skin and Moisturizers:
Chemistry and Function. CRC Press, Boca Raton, 2000: 311–325.
9Miller CC, Tang W, Ziboh VA et al. Dietary supplementation with
ethyl ester concentrates of fish oil (n-3) and borage oil (n-6)
polyunsaturated fatty acids induces epidermal generation of local
putative anti-inflammatory metabolites. J Invest Dermatol 1991;
96: 98–103.
10 Schurer NY. Implementation of fatty acid carriers to skin
irritation and the epidermal barrier. Contact Dermatitis 2002; 47:
199–205.
11 Sheu MY, Fowler AJ, Kao J et al. Topical peroxisome proliferator
activated receptor-alpha activators reduce inflammation in
irritant and allergic contact dermatitis models. J Invest Dermatol
2002; 118: 94–101.
12 Fowler AJ, Sheu MY, Schmuth M et al. Liver X receptor activators
display anti-inflammatory activity in irritant and allergic contact
dermatitis models: liver-X-receptor-specific inhibition of
inflammation and primary cytokine production. J Invest Dermatol
2003; 120: 246–255.
13 Lodén M, Andersson AC. Effect of topically applied lipids on
surfactant-irritated skin. Br J Dermatol 1996; 134: 215–220.
14 Komuves LG, Hanley K, Jiang Y et al. Ligands and activators of
nuclear hormone receptors regulate epidermal differentiation
during fetal rat skin development. J Invest Dermatol 1998; 111:
429–433.
15 Wright S, Burton JL. Oral evening-primrose-seed oil improves
atopic eczema. Lancet 1982; 2: 1120–1122.
16 Bamford JTM, Gibson RW, Renier CM. Atopic eczema
unresponsive to evening primrose oil (linoleic and gamma-
linolenic acids). J Am Acad Dermatol 1985; 13: 959–965.
17 Henz BM, Jablonska S, van de Kerkhof PCM et al. Double-blind,
multicentre analysis of the efficacy of borage oil in patients with
atopic dermatitis. Br J Dermatol 1999; 140: 685–688.
18 Hederos CA, Berg A. Epogam evening primrose oil treatment in
atopic dermatitis and asthma. Arch Dis Child 1996; 75: 494497.
19 Escobar SO, Achenbach R, Innantuono R et al. Topical fish oil in
psoriasis – a controlled and blind study. Clin Exp Dermatol 1992;
17: 159–162.
20 Dewsbury CE, Graham P, Darley CR. Topical eicosapentaenoic
acid (EPA) in the treatment of psoriasis. Br J Dermatol 1989; 120:
581.
Clinical Benefit of Moisturizers 11
© 2005 European Academy of Dermatology and Venereology JEADV (2005) 19, 000–000
21 Gupta AK, Ellis CN, Goldfarb MT et al. The role of fish oil in
psoriasis. A randomized, double blind, placebo-controlled study
to evaluate the effect of fish oil and topical corticosteroid therapy
in psoriasis. Int J Dermatol 1990; 29: 591–595.
22 Zepelin HHH-V, Mrowietz U, Färber L et al. Highly purified
omega-3-polyunsaturated fatty acids for topical treatment of
psoriasis. Results of a double-blind, placebo-controlled
multicentre study. Br J Dermatol 1993; 129: 713–717.
23 Hartop PJ, Allenby CF, Prottey C. Comparison of barrier function
and lipids in psoriasis and essential fatty acid-deficient rats. Clin
Exp Dermatol 1978; 3: 259–267.
24 Kibbe AW. Handbook of Pharmaceutical Excipients, 3rd edn.
American Pharmaceutical Association, Pharmaceutical Press,
Washington, London, 2000.
25 Barany E, Lindberg M, Lodén M. Unexpected skin barrier
influence from nonionic emulsifiers. Int J Pharm 2000; 195: 189–
195.
26 Imokawa G, Akasaki S, Hattori M et al. Selective recovery of
deranged water-holding properties by stratum corneum lipids.
J Invest Dermatol 1986; 87: 758–761.
27 Man MQ, Feingold KR, Elias PM. Exogenous lipids influence
permeability barrier recovery in acetone-treated murine skin. Arch
Dermatol 1993; 129: 728–738.
28 Rawlings AV, Harding C, Watkinson A et al. The effect of glycerol
and humidity on desmosome degradation in stratum corneum.
Arch D ermatol Res 1995; 287: 457–464.
29 Froebe CL, Simion FA, Ohlmeyer H et al. Prevention of stratum
corneum lipid phase transitions in vitro by glycerol–An alternative
mechanism for skin moisturization. J Soc Cosmet Chem 1990; 41:
51–65.
30 Mattai J, Froebe CL, Rhein LD et al. Prevention of model stratum
corneum lipid phase transitions in vitro by cosmetic additives –
Differential scanning calorimetry, optical microscopy, and water
evaporation studies. J Soc Cosmet Chem 1993; 44: 89–100.
31 Fluhr JW, Mao-Qiang M, Brown BE et al. Glycerol regulates
stratum corneum hydration in sebaceous gland deficient (asebia)
mice. J Invest Dermatol 2003; 120: 728–737.
32 Schmid-Grendelmeier P, Wyss M, Elsner P. Contact allergy to
dexpanthenol. A report of seven cases and review of the literature.
Dermatosen 1995; 43: 175–178.
33 Reynolds JEF. Martindale the Extra Pharmacopoeia, 30th edn. The
Pharmaceutical Press, London, 1993.
34 Final Report on the safety assessment of panthenol and
pantothenic acid. J Am Coll Toxicol 1987; 6: 139–163.
35 Laden K. Natural moisturization factors in skin. Am Perfum
Cosmet 1967; 82: 77–79.
36 Jacobi OK. Moisture regulation in the skin. Drug Cosmet Ind 1959;
84: 732–812.
37 Middleton J. Development of a skin cream designed to reduce dry
and flaky skin. J Soc Cosmet Chem 1974; 25: 519–534.
38 Wehr R, Krochmal L, Bagatell F et al. A controlled two-center
study of lactate 12% lotion and a petrolatum-based creme in
patients with xerosis. Cutis 1986; 37: 205–209.
39 Swanbeck G, Rajka G. Antipruritic effect of urea solutions. Acta
Derm Venereol 1970; 50: 225–227.
40 Rosten M. The treatment of ichthyosis and hyperkeratotic
conditions with urea. Aust J Dermatol 1970; 11: 142–144.
41 Dattner AM. From medical herbalism to phytotherapy in
dermatology: back to the future. Dermatol Ther 2003; 16: 106–113.
42 Shelton RM. Aloe vera. Its chemical and therapeutic properties. Int
J Dermatol 1991; 30: 679 683.
43 Andreassi M, Stanghellini E, Ettorre A et al. Antioxidant activity of
topically applied lycopene. J Eur Acad Dermatol Venereol 2004; 18:
52–55.
44 Lundstrom A, Egelrud T. Cell shedding from human plantar skin
in vitro: evidence of its dependence on endogenous proteolysis.
J Invest Dermatol 1988; 91: 340–343.
45 Denda M, Katagiri C, Hirao T et al. Some magnesium salts and
a mixture of magnesium and calcium salts accelerate skin barrier
recovery. Arch Dermatol Res 1999; 291: 560–563.
46 Ashida Y, Ogo M, Denda M. Epidermal interleukin-1 alpha
generation is amplified at low humidity: implications for the
pathogenesis of inflammatory dermatoses. Br J Dermatol 2001;
144: 238–243.
47 Morris-Jones R, Robertson SJ, Ross JS et al. Dermatitis caused by
physical irritants. Br J Dermatol 2002; 147: 270–275.
48 Cork MJ. The role of Staphylococcus aureus in atopic eczema:
treatment strategies. J Eur Acad Dermatol Venereol 1996; 7:
S31–S37.
49 Strange P, Skov L, Lisby S et al. Staphylococal enterotoxin B
applied on intact normal and intact atopic skin induces dermatitis.
Arch D ermatol 1996; 132: 27–33.
50 Ghadially R, Brown BE, Hanley K et al. Decreased epidermal lipid
synthesis accounts for altered barrier function in aged mice.
J Invest Dermatol 1996; 106: 1064–1069.
51 Garg A, Chren MM, Sands LP et al. Psychological stress perturbs
epidermal permeability barrier homeostasis: implications for the
pathogenesis of stress-associated skin disorders. Arch D ermatol
2001; 137: 53–59.
52 Werner Y, Lindberg M. Transepidermal water loss in dry and
clinically normal skin in patients with atopic dermatitis. Acta
Derm Venereol 1985; 65: 102–105.
53 Lodén M, Olsson H, Axell T et al. Friction, capacitance and
transepidermal water loss (TEWL) in dry atopic and normal skin.
Br J Dermatol 1992; 126: 137–141.
54 Thune P. Evaluation of the hydration and the water-holding
capacity in atopic skin and so-called dry skin. 1989; 144:
133–135.
55 Finlay AY, Nicholls S, King CS et al. The ‘dry’ non-eczematous
skin associated with atopic eczema. Br J Dermatol 1980; 103:
249–256.
56 Ghadially R, Reed JT, Elias PM. Stratum corneum structure and
function correlates with phenotype in psoriasis. J Invest Dermatol
1996; 107: 558–564.
57 Motta S, Monti M, Sesana S et al. Abnormality of water barrier
function in psoriasis. Arch D ermatol 1994; 130: 452–456.
12 Lodén
© 2005 European Academy of Dermatology and Venereology JEADV (2005) 19, 000–000
58 Elias PM, Schmuth M, Uchida Y et al. Basis for the permeability
barrier abnormality in lamellar ichthyosis. Exp Dermatol 2002; 11:
248–256.
59 Lavrijsen AP, Oestmann E, Hermans J et al. Barrier function
parameters in various keratinization disorders: transepidermal
water loss and vascular response to hexyl nicotinate. Br J Dermatol
1993; 129: 547–553.
60 Lavrijsen AP, Bouwstra JA, Gooris GS et al. Reduced skin barrier
function parallels abnormal stratum corneum lipid organization
in patients with lamellar ichthyosis. J Invest Dermatol 1995; 105:
619624.
61 Gånemo A, Virtanen M, Vahlquist A. Improved topical treatment
of lamellar ichthyosis: a double blind study of four different cream
formulations. Br J Dermatol 1999; 141: 1027–1032.
62 Grice K, Sattar H, Baker H. Urea and retinoic acid in ichthyosis
and their effect on transepidermal water loss and water holding
capacity of stratum corneum. Acta Derm Venereol 1973; 54: 114–
118.
63 Leveque JLGL, Grove GL, de Rigal J et al. Biophysical
characterization of dry facial skin. J Soc Cosmet Chem 1987; 82:
171–177.
64 Linde YW. ‘Dry’ skin in atopic dermatitis. A clinical study. Acta
Derm Venereol 1989; 69: 311–314.
65 Ginsburg IH. The psychosocial impact of skin disease. An
overview. Dermatol Clin 1996; 14: 473–484.
66 Serup J. EEMCO guidance for the clinical assessment of dry skin
(xerosis) and ichthyosis: clinical scoring systems. Skin Res Technol
1995; 1: 109–114.
67 Zachariae R, Zachariae H, Blomqvist K et al. Quality of life in 6497
Nordic patients with psoriasis. Br J Dermatol 2002; 146: 1006–
1016.
68 Kolbe L. Non-invasive methods for testing of the stratum corneum
barrier function. In: Lodén M, Maibach HI, eds. Dry Skin and
Moisturizers: Chemistry and Function. CRC Press, Boca Raton,
2000: 393–401.
69 Takenouchi M, Suzuki H, Tagami H. Hydration characteristics of
pathologic stratum corneum-evaluation of bound water. J Invest
Dermatol 1986; 87: 574–576.
70 Elias PM. Lipids and the epidermal permeability barrier. Arc h
Dermatol Res 1981; 270: 95–117.
71 Anderson RL, Cassidy JM, Hansen JR et al. Hydration of stratum
corneum. Biopolymers 1973; 12: 2789 –2802.
72 Blank IH. Further observations on factors which influence the
water content of the stratum corneum. J Invest Dermatol 1953; 21:
259–271.
73 Laden K, Spitzer R. Identification of a natural moisturizing agent
in skin. J Soc Cosm Chem 1967; 18: 351–360.
74 Imokawa G, Kuno H, Kawai M. Stratum corneum lipids serve as
a bound-water modulator. J Invest Dermatol 1991; 96: 845–851.
75 Jokura Y, Ishikawa S, Yamasaki S et al. Solid state 13C-NMR
studies on elastic property of the stratum corneum. 1992; 2:
715.
76 Horii I, Nakayama Y, Obata M et al. Stratum corneum hydration
and amino acid content in xerotic skin. Br J Dermatol 1989; 121:
587–592.
77 Sybert VP, Dale BA, Holbrook KA. Ichthyosis vulgaris:
identification of a defect in filaggrin synthesis correlated with an
absence of keratohyaline granules. J Invest Dermatol 1985; 84: 191–
194.
78 Marstein S, Jellum E, Eldjarn L. The concentration of
pyroglutamic acid (2-pyrrolidone-5-carboxylic acid) in normal
and psoriatic epidermis, determined on a microgram scale by gas
chromatography. Clinica Chim Acta 1973; 43: 389–395.
79 Vahlquist A. Ichthyosis – an inborn dryness of the skin. In: Lodén
M, Maibach HI, eds. Dry Skin and Moisturizers; Chemistry and
Function. CRC Press, Boca Raton, 2000: 121–133.
80 Scott IR, Harding CR. Filaggrin breakdown to water binding
compounds during development of the rat stratum corneum is
controlled by the water activity of the environment. Dev Biol 1986;
115: 84–92.
81 Williams H. Dowling oration 2001. Evidence-based dermatology
– a bridge too far? Clin Exp Dermatol 2001; 26: 714 –724.
82 Lodén M. The increase in skin hydration after application of
emollients with different amounts of lipids. Acta Derm Venereol
1992; 72: 327–330.
83 Nicholls S, King CS, Marks R. Short term effects of emollients and
a bath oil on the stratum corneum. J Soc Cosmet Chem 1978; 29:
617–624.
84 Garber CA, Nightingale CT. Characterizing cosmetic effects and
skin morphology by scanning electron microscopy. J Soc Cosmet
Chem 1976; 27: 509–531.
85 Jemec GB, Wulf HC. Correlation between the greasiness and the
plasticizing effect of moisturizers. Acta Derm Venereol 1999; 79:
115–117.
86 Suzuki Y, Nomura J, Koyama J et al. The role of proteases in
stratum corneum: Involvement in stratum corneum
desquamation. Arch Dermatol Res 1994; 286: 249–253.
87 Ohman H, Vahlquist A. The pH gradient over the stratum
corneum differs in X-linked recessive and autosomal dominant
ichthyosis: a clue to the molecular origin of the ‘acid skin mantle’?
J Invest Dermatol 1998; 111: 674677.
88 Lodén M. Urea-containing moisturizers influence barrier
properties of normal skin. Arch Dermatol Res 1996; 288:
103–107.
89 Lodén M, Andersson A-C, Lindberg M. Improvement in skin
barrier function in patients with atopic dermatitis after treatment
with a moisturizing cream (Canoderm®). Br J Dermatol 1999; 140:
264–267.
90 Elias PM, Menon GK. Structural and lipid biochemical correlates
of the epidermal permeability barrier. Adv Lipid Res 1991; 24: 1–
26.
91 Lucky AW, Leach AD, Laskarzewski P et al. Use of an emollient as
a steroid-sparing agent in the treatment of mild to moderate
atopic dermatitis in children. Pediatr Dermatol 1997; 14: 321–324.
92 Proksch E, Feingold KR, Man MQ et al. Barrier function regulates
epidermal DNA synthesis. J Clin Invest 1991; 87: 1668–1673.
Clinical Benefit of Moisturizers 13
© 2005 European Academy of Dermatology and Venereology JEADV (2005) 19, 000–000
93 Denda M, Wood LC, Emami S et al. The epidermal hyperplasia
associated with repeated barrier disruption by acetone treatment
or tape stripping cannot be attributed to increased water loss. Arch
Dermatol Res 1996; 288: 230–238.
94 Wood LC, Jackson SM, Elias PM et al. Cutaneous barrier
perturbation stimulates cytokine production in the epidermis of
mice. J Clin Invest 1992; 90: 482–487.
95 Van Scott EJ, Yu RJ. Control of keratinization with alpha-hydroxy
acids and related compounds. I. Topical treatment of ichthyotic
disorders. Arch Dermatol 1974; 110: 586–590.
96 Pope FM, Rees JK, Wells RS et al. Out-patient treatment of
ichthyosis: a double-blind trial of ointments. Br J Dermatol 1972;
86: 291–296.
97 Middleton JD, Roberts ME. Effect of a skin cream containing the
sodium salt of pyrrolidone carboxylic acid on dry and flaky skin. J
Soc Cosmet Chem 1978; 29: 201–205.
98 Frithz A. Investigation of Cortesal®, a hydrocortisone cream and
its water-retaining cream base in the treatment of xerotic skin and
dry eczemas. Curr Ther Res 1983; 33: 930–935.
99 Dahl MV, Dahl AC. 12% lactate lotion for the treatment of xerosis.
Arch D ermatol 1983; 119: 27–30.
100 Lodén M, Andersson AC, Anderson C et al. A double-blind study
comparing the effect of glycerin and urea on dry, eczematous skin
in atopic patients. Acta Derm Venereol 2002; 82: 45–47.
101 Kuster W, Bohnsack K, Rippke F et al. Efficacy of urea therapy in
children with ichthyosis. A multicenter randomized, placebo-
controlled, double-blind, semilateral study. Dermatology 1998;
196: 217–222.
102 Pigatto PD, Bigardi AS, Cannistraci C et al. 10% urea cream
(Laceran) for atopic dermatitis: a clinical and laboratory
evaluation. J Dermatol Treatment 1996; 7: 171–175.
103 Vilaplana J, Coll J, Trullás C et al. Clinical and non-invasive
evaluation of 12% ammonium lactate emulsion for the treatment
of dry skin in atopic and non-atopic subjects. Acta Derm Venereol
1992; 72: 28–33.
104 Kolbe L, Kligman AM, Stoudemayer T. Objective bioengineering
methods to assess the effects of moisturizers on xerotic leg of
elderly people. J Dermatol Treat 2000; 11: 241–245.
105 Andersson A-C, Lindberg M, Lodén M. The effect of two urea-
containing creams on dry, eczematous skin in atopic patients. I.
Expert, patient and instrumental evaluation. J Dermatol Treat
1999; 10: 165–169.
106 Lodén M, Andersson AC, Andersson C et al. Instrumental
and dermatologist evaluation of the effect of glycerine and
urea on dry skin in atopic dermatitis. Skin Res Technol 2001; 7:
209–213.
107 Serup J. A double-blind comparison of two creams containing
urea as the active ingredient. Assessment of efficacy and side-
effects by non-invasive techniques and a clinical scoring scheme.
Acta Derm Venereol Suppl 1992; 177: 34–43.
108 Proksch E, Nissen HP. Dexpanthenol enhances skin barrier repair
and reduces inflammation after sodium lauryl sulphate-induced
irritation. J Dermatol Treat 2002; 13: 173–178.
109 Fluhr JW, Gloor M, Lehmann L et al. Glycerol accelerates recovery
of barrier function in vivo. Acta Derm Venereol 1999; 79: 418– 421.
110 Mauro T, Holleran WM, Grayson S et al. Barrier recovery is
impeded at neutral pH, independent of ionic effects: implications
for extracellular lipid processing. Arch De rmatol Res 1998; 290:
215–222.
111 Buraczewska I, Lodén M. Treatment of surfactant-damaged skin
in humans with creams of different pH. Pharmacology 2004.
112 Lodén M, Lindberg M. The influence of a single application of
different moisturizers on the skin capacitance. Acta Derm Venereol
1991; 71: 79–82.
113 Wertz PW, Downing DT. Metabolism of topically applied fatty
acid methyl esters in BALB/C mouse epidermis. J Dermatol Sci
1990; 1: 33–38.
114 Moloney SJ. The in vitro percutaneous absorption of glycerol
trioleate through hairless mouse skin. J Pharm Pharmacol 1988;
40: 819–821.
115 Rawlings AV, Scott IR, Harding CR et al. Stratum corneum
moisturization at the molecular level. J Invest Dermatol 1995; 103:
731–740.
116 Tollesson A, Frithz A. Borage oil, an effective new treatment for
infantile seborrhoeic dermatitis. Br J Dermatol 1993; 129: 95.
117 Feingold KR, Brown BE, Lear SR et al. Effect of essential fatty acid
deficiency on cutaneous sterol synthesis. J Invest Dermatol 1986;
87: 588–591.
118 Held E, Lund H, Agner T. Effect of different moisturizers
on SLS-irritated human skin. Contact Dermatitis 2001; 44:
229–234.
119 Loden M. Barrier recovery and influence of irritant stimuli in skin
treated with a moisturizing cream. Contact Dermatitis 1997; 36:
256–260.
120 Kucharekova M, Schalkwijk J, Van de Kerkhof PCM et al. Effect
of a lipid-rich emollient containing ceramide 3 in experimentally
induced skin barrier dysfunction. Contact Dermatitis 2002; 46:
331–338.
121 Ghadially R, Halkier-Sorensen L, Elias PM. Effects of petrolatum
on stratum corneum structure and function. J Am Acad Dermatol
1992; 26: 387–396.
122 Lodén M, Barany E. Skin-identical lipids versus petrolatum in the
treatment of tape-stripped and detergent-perturbed human skin.
Acta Derm Venereol 2000; 80: 412–415.
123 Mortz CG, Andersen KE, Halkier-Sørensen L. The efficacy of
different moisturizers on barrier recovery in hairless mice
evaluated by non-invasive bioengineering methods. A model to
select the potentially most effective product. Contact Dermatitis
1997; 36: 297–310.
124 Thornfeldt C. Critical and optimal molar ratios of key lipids. In:
Lodén M, Maibach HI, eds. Dry Skin and Moisturizers: Chemistry
and Function. CRC Press, Boca Raton, 2000: 337–347.
125 Mao-Qiang M, Brown BE, Wu-Pong S et al. Exogenous
nonphysiologic vs. physiologic lipids. Divergent mechanisms for
correction of permeability barrier dysfunction. Arch Dermatol
1995; 131: 809–816.
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126 Zettersten EM, Ghadially R, Feingold KR et al. Optimal ratios of
topical stratum corneum lipids improve barrier recovery in
chronologically aged skin. J Am Acad Dermatol 1997; 37:
403–408.
127 Tollesson A, Frithz A. Transepidermal water loss and water content
in the stratum corneum in infantile seborrhoeic dermatitis. Acta
Derm Venereol 1993; 73: 18–20.
128 Chamlin SL, Kao J, Frieden IJ et al. Ceramide-dominant barrier
repair lipids alleviate childhood atopic dermatitis: changes in
barrier function provide a sensitive indicator of disease activity. J
Am Acad Dermatol 2002; 47: 198–208.
129 Halkier-Sorensen L, Thestrup-Pedersen K. The efficacy of a
moisturizer (Locobase) among cleaners and kitchen assistants
during everyday exposure to water and detergents. Contact
Dermatitis 1993; 29: 266–271.
130 Tabata N, O’Goshi K, Zhen YX et al. Biophysical assessment of
persistent effects of moisturizers after their daily applications:
evaluation of corneotherapy. Dermatology 2000; 200:
308–313.
131 Burr S. Emollients for managing dry skin conditions. Prof Nurse
1999; 15: 43–48.
132 Holden C, English J, Hoare C et al. Advised best practice for the use
of emollients in eczema and other dry skin conditions. J
Dermatolog Treat 2002; 13: 103–106.
133 Held E, Sveinsdottir S, Agner T. Effect of long-term use of
moisturizers on skin hydration, barrier function and susceptibility
to irritants. Acta Derm Venereol 1999; 79: 49–51.
134 Lodén M, Wessman C. The influence of a cream containing 20%
glycerin and its vehicle on skin barrier properties. Int J Cosmet Sci
2001; 23: 115–120.
135 Duval D, Lindberg M, Boman A et al. Differences among
moisturizers in affecting skin susceptibility to hexyl nicotinate,
measured as time to increase skin blood flow. Skin Res Technol
2002; 8: 1–5.
136 Hachem JP, De Paepe K, Vanpée E et al. The effect of two of
moisturisers on skin barrier damage in allergic contact dermatitis.
Eur J Dermatol 2002; 12: 136–138.
137 Berardesca E, Distante F, Vignoli GP et al. Alpha hydroxyacids
modulate stratum corneum barrier function. Br J Dermatol 1997;
137: 934–938.
138 Rawlings AV, Davies A, Carlomusto M et al. Effect of lactic acid
isomers on keratinocyte ceramide synthesis, stratum corneum
lipid levels and stratum corneum barrier function. Arch Der matol
Res 1996; 288: 383–390.
139 Gehring W, Gloor M. Effect of topically applied dexpanthenol on
epidermal barrier function and stratum corneum hydration.
Results of a human in vivo study. Arzneimittelforschung 2000; 50:
659–663.
140 Yunginger JW, Calobrisi SD. Investigation of the allergenicity of a
refined peanut oil-containing topical dermatologic agent in
persons who are sensitive to peanuts. Cutis 2001; 68: 153–155.
141 Cawley EP, Peterson NT, Wheeler CE. Salicylic acid poisoning in
dermatological therapy. JAMA 1953; 151: 372–373.
142 Drugs AAoP-Co. ‘Inactive’ ingredients in pharmaceutical
products: update (subject review). Pediatrics 1997; 99: 268–278.
143 Ernst E. Adverse effects of herbal drugs in dermatology. Br J
Dermatol 2000; 143: 923–929.
144 De Groot AC, Nater JP, Lende R et al. Adverse effects of cosmetics
and toiletries: a retrospective study in the general population. Int
J Dermatol Sci 1988; 9: 255–259.
145 Rietschel RL, Fowler JF. Fisher’s Contact Dermatitis, 4th edn.
Williams & Wilkins, Baltimore, 1995.
146 Ya-Xian Z, Suetake T, Tagami H. Number of cell layers of the
stratum corneum in normal skin – relationship to the anatomical
location on the body, age, sex and physical parameters. Arch
Dermatol Res 1999; 291: 555–559.
147 Frosch PJ, Kligman AM. A method for appraising the stinging
capacity of topically applied substances. J Soc Cosmet Chem 1977;
28: 197–209.
148 Gabard B, Nook T, Muller KH. Tolerance of the lesioned skin to
dermatological formulations. J Appl Cosmetol 1991; 9: 25–30.
149 Larmi E, Lahti A, Hannuksela M. Immediate contact reactions to
benzoic acid and the sodium salt of pyrrolidone carboxylic acid.
Contact Dermatitis 1989; 20: 38–40.
150 Fan W, Kinnunen T, Niinimäke A et al. Skin reactions to glycols
used in dermatological and cosmetic vehicles. Am J Contact
Dermat 1991; 2: 181–183.
151 Funk JO, Maibach HI. Propylene glycol dermatitis: re-evaluation
of an old problem. Contact Dermatitis 1994; 31: 236–241.
152 Lodén M, Andersson A-C, Lindberg M. The effect of two urea-
containing creams on dry, eczematous skin in atopic patients. II.
Adverse effects. J Dermatolog Treat 1999; 10: 171–175.
153 Khan SA. Treatment of non-inflammatory dermatoses. A double-
blind comparison of 1% hydrocortisone plus 10% urea and 0.05%
fluocinonide. Practitioner 1978; 221: 265–267.
154 Almeyda J, Fry L. Controlled trial of the treatment of atopic
eczema with a urea-hydrocortisone preparation versus
betamethasone 17-valerat. Br J Dermatol 1973; 88: 493–495.
155 Basketter D, Gerberick F, Kimber I et al. Contact irritation
mechanisms. In: Anderson D, Waters MD, Marrs TC, eds.
Toxicology of Contact Dermatitis. Allergy, Irritancy and Urticaria.
John Wiley and Sons, London, 1999: 11–38.
156 Blank IH. Factors which influence the water content of the stratum
corneum. J Invest Dermatol 1952; 18: 433–440.
157 Tsai TF, Maibach HI. How irritant is water? An overview. Contact
Dermatitis 1999; 41: 311–314.
158 Tupker RA, Willis C, Berardesca E et al. Guidelines on sodium
lauryl sulfate (SLS) exposure tests. A report from the
Standardization Group of the European Society of Contact
Dermatitis. Contact Dermatitis 1997; 37: 53–69.
159 Aungst BJ. The influence of fatty acids and fatty alcohols on skin
permeability. In: Lodén M, Maibach HI, eds. Dry Skin and
Moisturizers: Chemistry and Function. CRC Press, Boca Raton,
2000: 299–325.
160 Donbrow M, Azaz E, Pillersdorf A. Auto-oxidation of
polysorbates. J Pharm Sci 1978; 67: 1676–1681.
Clinical Benefit of Moisturizers 15
© 2005 European Academy of Dermatology and Venereology JEADV (2005) 19, 000–000
161 Loden M, Buraczewska I, Edlund F. The irritation potential and
reservoir effect of mild soaps. Contact Dermatitis 2003; 49:
91–96.
162 Lodén M, Buraczewska I, Edlund F. Irritation potential of
shower oils before and after use. Br J Dermatol 2004; 150:
1142–1147.
163 De Groot AC. Sensitizing substances. In: Lodén M, Maibach HI,
eds. Dry Skin and Moisturizers: Chemistry and Function. CRC
Press, Boca Raton, 2000: 403–411.
164 Barany E, Lodén M. Content of fragrance mix ingredients and
customer complaints of cosmetic products. Am J Contact Dermat
2000; 11: 74–79.
165 Jansson T, Lodén M. Strategy to decrease the risk of adverse effects
of fragrance ingredients in cosmetic products. Am J Contact
Dermat 2001; 12: 166–169.
166 Directive 2003/15/EC of the European Parliament and of the
Council of 27 February 2003. Amending Council Directive 76/
768/EEC on the approximation of the laws of the Member States
relating to cosmetic products. In: Official Journal of the European
Union 2003; 66: 27–35.
167 Howlett S. Emotional dysfunction, child–family relationships and
childhood atopic dermatitis. Br J Dermatol 1999; 140: 381–384.
168 Schlagel CA, Sanborn EC. The weights of topical preparations
required for total and partial body inunction. J Invest Dermatol
1964; 42: 253–256.
169 Lynfield YL, Schechter BA. Choosing and using a vehicle. J Am
Acad Dermatol 1984; 10: 56–59.
170 Ivens UI, Steinkjer B, Serup J et al. Ointment is evenly spread on
the skin, in contrast to creams and solutions. Br J Dermatol 2001;
145: 264–267.
171 Rhodes LE, Diffey BL. Fluorescence spectroscopy: a rapid,
noninvasive method for measurement of skin surface thickness of
topical agents. Br J Dermatol 1997; 136: 12–17.
172 Johnson R, Nusbaum BP, Horwitz SN et al. Transfer of topically
applied tetracycline in various vehicles. Arch Dermatol 1983; 119:
660–663.
The clinical benefit of moisturizers
Appendix A: CME questions
1. Ingredients typically found in moisturizers include:
(a) water, botanical extracts, fragrances
(b) lipids, preservatives, emulsifiers
(c) vegetable oils, silicones, EDTA
(d) humectants, oils, nickel
2. Which ingredient is essential to add to improve a form-
ulation already containing water, fragrance, vegetable oil,
petrolatum, EDTA?
(a) preservatives
(b) emulsifiers
(c) humectant
(d) all of the above
3. Which humectant has been found to improve skin barrier
function?
(a) sorbitol
(b) PCA
(c) urea
(d) propylene glycol
4. Which of the following substance can not be found both in
moisturizers and in the skin?
(a) propylene glycol
(b) stearic acid
(c) cholesterol
(d) vitamin E
5. What type of formulations can be used to treat dry skin?
(a) oil-in-water emulsions
(b) water-in-oil formulations
(c) bath-oils
(d) all of the above
6. Which is the most commonly found emulsion-type and
why is it popular?
(a) water-in-oil due to its efficiency
(b) oil-in-water due to its cosmetic elegance
(c) oil-in water due to its efficient occlusion
(d) water-in-oil due to easiness to use herbal
extracts
7. Why is the water barrier property of SC important?
(a) the body water reservoir can be depleted
(b) elevated evaporation can induce eczema
(c) skin friction is affected
(d) all of the above
8. Why do moisturizers contain preservatives?
(a) to allow for contamination during use
(b) to prevent growth of microorganisms on the skin
(c) to reduce decomposition of ingredients
(d) to provide good odour to the body
9. Which is the most commonly encountered adverse
reaction from moisturizers?
(a) contact allergy
(b) phototoxicity
(c) stinging
(d) erythema
10. Which substance does not belong to the natural
moisturizing factor (NMF)?
(a) glycerol
(b) lactic acid
(c) urea
(d) PCA
16 Lodén
© 2005 European Academy of Dermatology and Venereology JEADV (2005) 19, 000–000
11. What is the primary function of lipids in moisturizers?
(a) to reduce water evaporation
(b) to counteract release of cytokines
(c) to prevent absorption of noxious substances
(d) to provide the skin with calories
12. Why are antioxidants used in moisturizers?
(a) to decrease inflammation in the skin
(b) to increase the stability of the formulation
(c) to protect from UV radiation
(d) to give claim support
13. What is the potential adverse effect from bath/shower
oils?
(a) may influence the eyes and cause headache
(b) may affect the lungs
(c) may cause a slippery bath tub
(d) may contain irritants, which could delay normalization
of dry skin
14. What effect on the barrier function do moisturizers
have?
(a) increase TEWL
(b) decrease TEWL
(c) no change in TEWL
(d) all of the above
15. Name one potential advantage with vegetable oils
compared to petrolatum.
(a) more stable
(b) does not contain sensitizing impurities
(c) may influence the chemical composition of barrier
lipids,
(d) cheap
16. What quantity of moisturizer is reasonable to use in
individuals with dry skin?
(a) 20 mg per sq cm and application
(b) 2 kg/months
(c) 0.2 mg per sq cm and application
(d) none of the above
17. Which is the most common sensitizing agent in
moisturizers?
(a) nickel
(b) lanolin
(c) fragrances
(d) colour
18. What is the advantage with glycerol?
(a) no risk for sensitization
(b) may be appropriate for treatment of sebaceous gland
deficient areas
(c) may promote desquamation
(d) all of the above
19. Why is methyl paraben known for?
(a) low risk for sensitization
(b) efficient humectant
(c) good emulsifier
(d) good odour
Answers
1. (b) Botanical extracts, silicones, EDTA, and nickel are not
common in moisturizers.
2. (b) If the formulation already contains water and oils, then
it is necessary to include emulsifiers to obtain stability.
Preservatives may also be needed, but may not be necessary
if other precautions are taken to avoid microorganisms.
3. (c)
4. (a) Stearic acid can be found in the bilayer lipids together with
cholesterol. Vitamin E is an antioxidant in epidermis and dermis.
5. (d)
6. (b) Oil-in-water emulsions usually gives better cosmetic
feel, due to its often lower lipid content and less greasiness.
7. (d)
8. (a)
9. (c)
10. (a)
11. (a)
12. (b) Antioxidants are mainly used to prevent ingredients
from oxidation.
13. (d)
14. (d)
15. (c) Vegetable oils are usually less stable, may contain
sensitizers and are often more expensive than petrolatum.
16. (b)
17. (c)
18. (d)
19. (a) Very common preservative, with a very low risk of
contact allergy.
Clinical Benefit of Moisturizers 17
© 2005 European Academy of Dermatology and Venereology JEADV (2005) 19, 000–000
Information on author
Marie Lodén, Pharm, Dr Med Sc, associate professor, is the head of the Research and Develop-
ment of the dermatological company, ACO Hud Nordic AB in Stockholm, Sweden. She obtained
her pharmacist degree in 1980 from Uppsala University and was appointed associate professor
in experimental dermatology in 2004. She started her dermatological research with chemical warfare
agents at the National Defense Research Institute and continued with development of topical
products at a pharmaceutical company in Sweden. In 1992 she assumed her present position.
Dr Lodén is a member of several national and international societies like the International
Society for Bioengineering and the Skin, and acts in the committee of the European Group of
Efficacy Measurements of Cosmetics and other Topical Products (EEMCO).
Dr Lodén’s major research interests are skin barrier function, contact dermatitis, skin care,
biophysical measurements and toxicology, and has published about 70 peer-reviewed articles
and reviews.
... There is a growing body of literature that recognizes the importance of moisturizers. It is essential for a wide range of fields, such as cosmetics and pharmacy [1]. Moisturizers are very popular dermatological products prescribed due to their proven efficiency to prevent and treat various dermatological conditions [2,3]. ...
... Moisturizers are widely used for both normal and dry skin [1]. Application of these preparations can increase the water content in the stratum corneum, hence exerting its most vital action, which is moisturizing action aside from maintaining a normal skin pH, and allowing the lipid bilayers in the skin to more easily normalize and re-establish their capacity to connect corneocytes together and allow for moisture retention in the intercellular spaces [1,5,6]. ...
... Moisturizers are widely used for both normal and dry skin [1]. Application of these preparations can increase the water content in the stratum corneum, hence exerting its most vital action, which is moisturizing action aside from maintaining a normal skin pH, and allowing the lipid bilayers in the skin to more easily normalize and re-establish their capacity to connect corneocytes together and allow for moisture retention in the intercellular spaces [1,5,6]. Subsequently, the hydration interrupts the dry skin cycle, making the skin surface smooth, soft, pliable and more extensible [1,6]. ...
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Moisturizers are one of the most widely used preparations in cosmetics and have been extensively used to soften the skin for consumers. Moisturizers work effectively in combating dry skin which may cause pain, tightness, itch, stinging, and/or tingling. The aim of this review is to evaluate published studies on the history, ingredients, preparation processes, characteristics, uses, and applications of moisturizers. Moisturizers bridge the gap between medicine and consumer goods by being used to make the skin more beautiful and healthy. In the future, in moisturizer therapy, the capacity to adapt specific agents to specific dermatological demands will be crucial. Cosmetically, moisturizers make the skin smooth by the mechanism of increasing the water content in the stratum corneum, hence exerting its most vital action, which is moisturizing action and maintaining a normal skin pH.
... При снижении увлажнения кожи нарушаются процессы десквамации чешуек за счет изменения активности гидролитических ферментов и скорости реакций разрушения связей между корнеоцитами. Возникает шелушение и изменяется проницаемость кожи [1,22]. ...
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The review summarizes information about the main causes and pathogenesis of xerosis cutis as one of the conditions indicating a violation of the epidermal barrier. Xerosis cutis is a clinical sign of a decrease in the amount and/or quality of lipids and/or hydrophilic substances in the stratum corneum of the epidermis. The modern approach to the treatment of dermatoses accompanied by violations of the epidermal barrier includes basic moisturizers. Urea not only moisturizes the skin. It is involved in the regulation of barrier function and antimicrobial protection. It is a low-molecular regulator of protein synthesis in keratinocytes, such as filaggrin, loricrin, involucrin and transglutaminase 1, cathelicidin, beta-defensin-2, water and urea carrier proteins into the cell, as well as proteins that promote the synthesis of intercellular matrix lipids. The main dermatotropic pharmacological effects of urea (hydration of the epidermis, strengthening of the barrier function of the skin, keratolytic effect, increased penetration of drugs into the skin) have been used in dermatological practice for many years. External agents with urea are used to treat skin diseases accompanied by dryness and excessive keratinization, to correct the deformation of nail plates of various genesis, to facilitate the local penetration of medicines. The use of topical UrocrEM5, UrocrEM10, Uroderm ointments containing 5%, 10% and 30% urea, respectively, is effective and safe.
... Panthenol and butylene glycol also possess humectant properties [26,27] and are functional ingredients in the majority of äKwä products. Occlusives such as beeswax and oils function as a skin barrier to prevent moisture loss [25]. ...
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Skin dryness, fine lines and wrinkles, red spots, red vasculature, and porphyrin count are common indicators of skin health and beauty. The skincare system in this study contains scientifically validated ingredients such as fermented green tea (Camellia sinensis) water, niacinamide, antioxidants, and a variety of natural plant extracts. The purpose of this study was to evaluate the effectiveness of this skincare system in improving facial-skin health and beauty. Twenty-six healthy adults, both female and male, aged 18–54 and of all skin types and tones, were included in the study and participated as either the active or the control group (competitor product) using designated topical products for 30 days. Skin moisture, fine lines and wrinkles, porphyrin count, red spots, and red vasculature count were measured through high-quality photography, Visia® complexion analysis, FitSkin® skin analysis, and survey questions on day 0, day 8, and day 30. Significant improvements were observed in facial moisture, red-spot count, red vasculature count, and porphyrin count on day 30 in comparison with the control group. Non-significant improvements were observed in pores, skin texture, and wrinkles. With extensive well-documented functional ingredients, the studied skincare system used daily may significantly improve key areas of skin health and beauty.
... Moisturizers with bioactive compounds provide moisture to the skin and can be used to treat dermatological diseases [4]. They must preserve the optimal balance between water and skin lipids by maintaining the water content in the skin. ...
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Sea buckthorn (SB) (Elaeagnus rhamnoides (L.) A. Nelson) is rich in flavonoids, phenolic compounds, anthocyanins, carotenoids, and phytosterol. Its phytochemicals exhibit various biological activities, such as antioxidant, immunomodulatory and anti-carcinogenic activities. SB also helps prevent the development of wrinkles and protects the skin’s surface from UV rays. The purpose of the present study was to develop and characterize an SB oil (SBO)-loaded nanostructured lipid carrier (NLC) for improved skin hydration. The response surface methodology (RSM) and central composite design (CCD) were employed to optimize the influencing factors (wax percentage, surfactant percentage, and PEG400 percentage in the surfactant) to achieve the desirable qualities in SBO-NLCs. The optimum (minimum) size of SBO-NLCs (105.26 nm) was obtained with a combination of 2.5% wax, 7.5% surfactant, and 30% PEG400 in the surfactant. A narrow polydispersity index (PDI; 0.16), relatively low zeta potential (ZP; 􀀀15.63 mV), and high entrapment efficiency (EE; 90.88%) were observed in this study. Reduced quadratic and reduced 2FI models were adapted to predict conditions to attain the optimum size and PDI of SBO-NLCs, respectively. ZP and EE were predicted with the help of a reduced cubic model. All of the predicted models were statistically significant. Differential scanning calorimetry results suggested that the SBO-NLCs had less crystallinity and therefore reduced the rate of drug expulsion from the inner core of the NLCs. A noticeable level of occlusion effect was observed in the SBO-NLCs. The SBO-NLCs showed a faster vitamin E (biomarker for the drug) release rate into the skin within 24 h, and the released vitamin E level after 48 h was significantly higher than that for the free SBO. Additionally, SBO-NLCs delivered vitamin E into the inner skin significantly (22.73 micro g/cm2 of skin). In conclusion, the SBO-NLC is a potential delivery system that can be used to prevent skin water loss and improve skin hydration. Further investigations, such as drug stability and safety evaluations, are required prior to commercialization for human use.
... Most guidelines recommend the use of emollients in conjunction with topical corticosteroids (TCS) for the initial treatment of this intractable disease. Moisturizer is used synonymously with emollient and refers to as a product that moisturizes and smooths the skin, whereas humectant increases or maintains hydration of the skin [18]. Dexpanthenol is a stable alcohol analog of pantothenic acid (vitamin B5) with moisturizing and wound healing efficacy. ...
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Background: Atopic dermatitis (AD) is an inflammatory skin disease of multiple phenotypes and endotypes, and is highly prevalent in children. Many people of all ages, including active adolescents, pregnant women, and the elderly, suffer from AD, experiencing chronicity, flares, and unexpected relapse. Dexpanthenol has multiple pharmacological effects and has been employed to treat various skin disorders such as AD. We aimed to summarize the up-to-date evidence relating to dexpanthenol and to provide a consensus on how to use dexpanthenol effectively for the treatment of AD. Methods: The evidence to date on the application and efficacy of dexpanthenol in AD was reviewed. The literature search focused on dexpanthenol use and the improvement of skin barrier function, the prevention of acute flares, and its topical corticosteroid (TCS) sparing effects. Evidence and recommendations for special groups such as pregnant women, and the effects of dexpanthenol and emollient plus in maintenance therapy, were also summarized. Results: Dexpanthenol is effective and well-tolerated for the treatment of AD. Dexpanthenol improves skin barrier function, reduces acute and frequent flares, has a significant TCS sparing effect, and enhances wound healing for skin lesions. Conclusion: This review article provides helpful advice for clinicians and patients on the proper maintenance treatment of AD. Dexpanthenol, as an active ingredient in ointments or emollients, is suitable for the treatment and maintenance of AD. This paper will guide dermatologists and clinicians to consider dexpanthenol as a treatment option for mild to moderate AD.
... When the concentration is less than 10%, it has a moisturizing effect, and when it is higher than 10%, it shows a keratolytic effect. Urea is used as a 10% cream for the treatment of ichthyosis and hyperkeratotic skin disorders, and in lower concentrations for the treatment of less severe dryness [38][39][40]. However, it may sting even at a concentration of less than 10%, so the face and sensitive areas should be avoided, and it is not a suitable moisturizer for children. ...
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As interest in skin increases, the cosmetic market is also growing. It is difficult to choose between the numerous types of basic cosmetics on the market. This article aims to provide advice and guidance on which products to recommend according to a patient’s skin condition. Appropriate application of a moisturizer attempts not only to improve the dryness, but also improve the skin’s natural barrier function to protect the skin from internal and external irritants to keep the skin healthy. Moisturizers consist of various ingredients, including occlusive agents, emollients, humectants, lipid mixture, emulsifiers, and preservatives. Pathophysiology of dry skin is also discussed to provide readers with the background they need to choose the right moisturizer for themselves. As moisturizers play an important role as adjuvant in the treatment of common skin diseases, such as atopic dermatitis, contact dermatitis, psoriasis, acne and rosacea, which type of moisturizer is appropriate for each disease was also dealt with. Basic cosmetics, especially moisturizers, should be recommended in consideration of the ingredients, effectiveness and safety of each product, and the skin condition of each patient.
... Topical moisturizers, as the most widely used components of basic skin care (5), increase skin hydration by preventing water loss from the skin surface, which is known as "moisturizing from the outside." Moisturizers are safer in contrast to conventional medicines utilized by doctors (6,7). Nevertheless, uncomfortable skin reactions from topical preparations, like sensory reactions or subjective sensations (no signs of inflammatory events), may still be encountered after application (7)(8)(9). ...
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Background: The dietary supplement industry offers many oral cosmetics that purportedly assist in skin moisturization often with unclear evidence supporting efficacy and safety. To update the accessible proofs pertaining to the safety and effectiveness of oral dietary supplements to facilitate skin moisturizing via an all-around review and meta-analysis. Methods: Three on-line databases [Pubmed, Embase, and Cochrane Library (CENTRAL)] were retrieved from January 2000 to November 2021. An overall 66 randomized controlled trials (RCTs) of skin care were recognized. Meta-analysis was performed for dietary supplements with four or more available research. Results: Oral collagen or ceramide resulted in a statistically significant increase in skin hydration and a decrease in transepidermal water loss (TEWL) compared to placebo. No benefits regarding the improvement of skin conditions in terms of water content and TEWL were observed for lactic acid bacteria or Lactobacillus fermented foods. A statistically significant and positive effect on skin hydration was observed for both hyaluronan and procyanidin, with an unknown effect on TEWL due to insufficient RCTs. There was a non-significant improvement in the water content of stratum corneum for astaxanthin based on subgroup analyses. Among the dietary supplements trialed in ≤ 3 RCTs, the judgment regarding their effects on skin moisturizing was prevented by inconsistent conclusions as well as insufficient research. All food supplements were safe throughout the research (normally ≤ 24 weeks). Conclusion: Oral dietary supplements, including collagen, ceramides, hyaluronan, and procyanidin, were proven to be effective for skin moisturization. At present, for skin moisturization, the proofs supporting the recommendation of other dietary supplements, such as lactic acid bacteria and astaxanthin, are insufficient. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/ identifier CRD42021290818.
Article
Objectives Comedogenicity is a critical factor in making of cosmetics and skin care products. The term “acne cosmetica” was coined to link the relationship between female acne to the use of cosmetic formulations, stating that the ingredients used in the cosmetic formulations have the potential to evoke a comedogenic response or produce comedones. Therefore, it is important that a skin care product is non-comedogenic and efficacious at the same time. The main objective of this study is to evaluate the comedogenic potential of the test product (Venusia Max Cream – paraben free) when applied topically under occluded patch to the skin. Material and Methods This was a randomized, double-blinded, comparative study conducted in 24 healthy female participants, with prominent follicular orifices on the upper back region. Comedogenic potential of the test product (Venusia Max Cream – paraben free) was evaluated in comparison to positive (coconut oil) and negative (glycerin) controls in women. Each participant received topical application of test and control products under occluded patch to the skin on the upper aspect of the back, 3 times weekly for 4 weeks. Cyanoacrylate biopsies were performed before and after treatment to determine the microcomedones histologically. Microcomedones were graded using light microscopy and results were analyzed based on scale rating (0–3). Results The mean comedone grading was assessed between positive versus negative control, and positive control versus test product. The mean comedone grades were significantly less in test product 0.41 ± 0.50 and negative control 0.82 ± 0.73 in comparison to positive control 2.09 ± 0.68. The test product was least comedogenic in this study. Furthermore, no adverse events were reported during the study period. Conclusion Based on the histological evidence, Venusia Max Cream (paraben free) is a non-comedogenic, plant-based intense moisturizing cream and its use in regular skin care routine can be beneficial, particularly for acne prone and dry skin as it improves the skin hydration levels.
Article
Background: Moisturizers play an important role in restoring the skin barrier. They should be used to treat and prevent eczema, especially in atopic dermatitis (AD). Objective: To evaluate the factors that influence selection of moisturizers in adult patients with AD and without it. Usage behavior between the two groups was also determined. Methods: A cross-sectional web-based survey was performed. Results: A total of 1,195 participants with mean age of 46.5 ± 14.5 were enrolled. Fifty participants (4.2%) met the William's criteria for AD diagnosis. Most participants reported using moisturizer every day or two times per day. A non-sticky moisturizer, followed by pleasant odor were considered important properties. For choosing a moisturizer, personal satisfaction was the most common answer given by participants. The most common locations that participants applied moisturizer were the extremities (85.1%) and face (84.9%). Physicians' suggestion was also a significant factor that led to moisturizer use by AD patients but it was not significant in the non-AD group (29.2% vs 14.7%, p = 0.007, OR 2.4). A pH of 5.5 and the anti-inflammatory property were important factors in choosing a moisturizer in the AD group. Both AD and non-AD participants preferred liquid soap over bar soap in daily life. Conclusions: Our results showed that most participants have basic knowledge of how to use a moisturizer. Physicians' suggestion influenced the selection of moisturizer in AD patients. Thus, physicians should continue to educate in order to achieve good clinical outcomes.
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The essential role of water in elasticity of the stratum corneum (SC) has been well acknowledged, while water-holding property of the SC is mainly associated with natural moisturizing factors (NMF) and intercellular lipids. Because available evidence indicates that water itself has no substantial capacity of increasing elasticity in the SC depleted of NMF, it has been speculated that a specific intermolecular interaction between keratin fibers and NMF is required for the complete achievement of elasticity due to association with water molecules. In order to elucidate precise molecular mechanisms underlying SC elasticity, we have measured the molecular dynamics of chemical residues within keratin fibers of human plantar SC under various conditions by cross polarization/magic angle spinning (CP/MAS) 13C-NMR technique in which the elasticity of keratin fibers can be evaluated by comparing the intensities of their NMR spectra.The intensities of NMR spectra responsible for amide bond-carbonyl, Cα methine and sidechain aliphatic carbons in the intact SC were found to decrease markedly with increasing water content up to 30% of dry SC and then to reach a constant value over 30%. Lipid extraction of intact SC with acetone/ether (1/1) did not induce any significant change in the NMR spectrum, whereas an additional treatment with water that releases NMF consisting mainly of amino acids, caused the SC to lose elasticity as revealed by significantly increased intensity of the spectrum even in the presence of excess water. The observed decrease in elasticity of the SC was found to recover after treatment with basic and neutral amino acids, but not with acidic amino acid. Parallel studies for complex modulus on elasticity of SC sheet by the rheovibron also demonstrated that removal of NMF reduces elasticity of the SC whose effect is reversible with the application of basic and neutral amino acids. These findings suggest that structural proteins mainly consisting of keratin acquire their elasticities by reducing intermolecular forces between keratin fibers with the help of hydrated NMF.
Book
The previous edition of Dry Skin and Moisturizers: Chemistry and Function was the first book devoted to all aspects of moisturizers, a subject often given short shrift in dermatology texts. It quickly became a standard reference. In the past five years, there has been an explosion of new information relating to the nature of dry skin and its treatm