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What evidence is there for moisturisers?


A review of the available evidence for various ingredients in products recommended
as moisturisers in dry skin conditions. This article is intended to accompany a CPD
article on the mechanisms involved in dry skin conditions published on 2 April 2011
Rod Tucker, PhD, MRPharmS, community pharmacist

Given the widespread use of moisturisers The importance of glycerol in skin


there are surprisingly few good quality studies hydration has been clearly demonstrated in
of ecacy in patients. Some studies show that rodent studies in which animals lacking the
some of the more common ingredients used AQP3 channels have dry skin. Topical and oral
do increase skin hydration or improve the administration of glycerol improved dry skin
barrier function of the skin (ie, reduce and a similar eect has been suggested in
transepidermal water loss; TEWL). However, humans. The hydrating eect of topical
even where studies exist, one of the problems glycerol has been shown to be maintained over
for investigators is the lack of a standardised six weeks compared with placebo.
denition of dry skin that can be measured Another role of glycerol is that it aids
objectively. In addition, studies tend to be desquamation and one study, although in vitro,
small often with around 30 subjects. showed that it increased the rate of corneocyte
Many studies use changes or dierences in loss by facilitating corneodesmosome
TEWL or capacitance as measures of breakdown.
eectiveness, but changes in symptom scores However, there are few good quality
are often a better indicator. TEWL is not a clinical trials of glycerol in patients with dry
sensitive measure and has been shown to skin conditions. In 2008, a randomised, Martin Novak /Dreamstime.com
either increase or decrease after the double-blind prospective study in patients
application of various moisturisers. Indeed, with mild-to-moderate atopic eczema found Reflect
improvement in symptoms does not always that application of a 20 per cent glycerol
correlate with a reduction in TEWL. Some cream improved skin hydration compared
studies in people with xerotic skin have with placebo but there was no signicant
included visual analogue scales and expert dierence in erythema and SCORAD (an
assessment in addition to the biometric eczema severity score) values between the
methods as part of the evaluation process. glycerol group and the control group.1 Evaluate Plan
An earlier double-blind trial in 197 patients
Glycerol with atopic eczema found a 20 per cent
Glycerol (glycerin) is an old-fashioned glycerol cream to be equivalent to a cream
humectant widely used in cosmetic containing both urea (4 per cent) and sodium
preparations. It also occurs naturally in skin chloride (4 per cent) but that the glycerol
and is transported to the stratum corneum via cream produced less smarting.2 Findings were Act
aquaporin 3 (AQP3) channels, which are based on patient self-reporting and
membrane based transporter molecules in the independent evaluation by a dermatologist.
basal keratinocyte layer. Although there were no signicant dierences
in dryness scores between the two groups, 11 REFLECT
per cent of patients in the urea group reported
drier skin after using the urea. In another 1 Which ingredients in moisturiser products
KEY POINTS clinical study in atopic patients by the same have evidence of efficacy?
researchers, it was found that the same urea 2 What is the rationale for using oatmeal
There is a lack of good quality clinical trials cream (rather than the glycerol) provided extracts for dry skin conditions?
on moisturising products but there is greater reduction in TEWL and lower 3 Are you confident of the advice you give to
evidence of benefit from using moisturisers aggregated dryness scores.3 The authors noted people with dry skin?
in eczema and psoriasis. that the changes in skin capacitance were not
Alpha hydroxy acids (eg, lactic acid) appear dierent for the two test creams and results Before reading on, think about how this article
to have an effect on desquamation, making with the glycerin cream were not signicantly may help you to do your job better.
them helpful in scaling conditions. dierent to placebo.
Some evidence suggests that long-term use A recent study found glycerol to be
of moisturisers on normal skin may have benecial in reducing the irritation from
adverse effects, such as increased surfactant induced contact dermatitis.4
sensitivity to irritants. and reducing scaling associated with
Aqueous cream should not be considered Urea dry skin.5
as a first-line, leave-on emollient. Urea is an ingredient seen in many In a study of patients with atopic eczema, it
Newer moisturisers are beginning to include moisturisers, including Balneum and E45 Itch was found that twice daily application of 5 per
barrier repair lipids (eg, ceramides). Relief (5 per cent), Aquadrate, Calmurid, cent urea for 20 days reduced TEWL and the
Patients with dry skin conditions should be Eucerin Intensive and Hydromol Intensive (10 susceptibility of the skin to sodium lauryl
given a wide choice of products to per cent) and Dermatonics Heel Balm (25 per sulphate (ie, barrier function was improved).6
encourage frequent use. cent). A double-blind comparison of two In another study a 10 per cent cream reduced
creams containing 3 or 10 per cent urea found TEWL and improved the itching and dryness
both equally eective at increasing hydration associated with atopic eczema.7

April 2011
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A randomised, double-blind trial in


children with ichthyosis found that a 10 per PANEL 1: RECENT FDA APPROVED MOISTURISERS
cent lotion improved the clinical signs of the
condition based on a visual analogue scale, but
the dierences were small8 (78 per cent EpiCeram EpiCeram Skin Barrier Emulsion is a mixture of ceramides, cholesterol and fatty acids,
response rate vs 72 per cent in the placebo) mimicking those in the skin. Two studies have reported on its effects. One was published as a full
and the results of the capacitance paper but the second is available only as an abstract. The first compared EpiCeram against
measurements were similar. fluticasone proprionate in children with moderate-to-severe atopic eczema. The results showed
A urea based lotion was also found to that, although fluticasone produced a faster response, the difference was not significant after 28
reduce the symptoms of dry skin and itching days of therapy.20 The second study was prospective, randomised and investigator blinded. It
in a randomised, double-blind study compared EpiCeram with pimecrolimus in 38 children with mild-to-moderate eczema. The primary
compared with the vehicle base in aged skin.9 outcome measure was the change in EASI scores (an eczema severity scale). After four weeks, the
pimecrolimus group achieved a median reduction in EASI score of 2.0 compared with 1.2 for
Oatmeal extracts pimecrolimus but this difference was reported as not significant.21
Some evidence exists to show that colloidal EpiCeram is not currently available in the UK.
oatmeal is eective in the management of dry
skin. Colloidal oatmeal contains lipids, Atopiclair The ingredients of Atopiclair are botanical and include glycyrrhetinic acid (from
proteins and polysaccharides and when liquorice), grape seed oil and shea butter. The product was approved for atopic dermatitis, contact
dispersed in water, it forms a viscous occlusive dermatitis and dry skin. There are three published randomised, double-blind vehicle-controlled
barrier and the hydrophilic polysaccharides trials in patients with atopic eczema, all of which show superiority of Atopiclair.2224 Presumably the
absorb water, creating a humectant eect. The efficacy is based on a combined effect of the components so the use of a valid vehicle control in
proteins present also provide a buering trails is difficult. This product, which also contains hyaluronic acid, is available in the UK.
action, which helps to lower skin pH in
pruritic conditions. One study using an MimyX MimyX contains the fatty acid N-palmitoyl ethanolamine, a potent agonist of cannabinoid
oatmeal lotion (Aveeno) in patients with receptors on mast cells. Cannabinoid receptors are also present on keratinocytes. N-palmitoyl
itching due to skin lesions and dryness found ethanolamine exhibits strong anti-inflammatory effects in animal models. It was approved for the
that the lotion provided relief of symptomatic management of atopic dermatitis, allergic contact dermatitis and radiation dermatitis. Although
itch in over 80 per cent of patients.10 there are no published clinical studies available on the product itself, one study of N-palmitamoyl
There is some evidence that oatmeal ethanolamine in mild-to-moderate atopic eczema found patients reported a reduction in pruritus
extract reduces release of arachidonic acid and skin dryness, and that scaling was reduced.25 MimyX is not currently available in the UK.
from phospholipids, suggesting an anti-
inammatory eect. In particular, in 2005, a
study using avenanthramides (phytochemicals
found in oatmeal) showed that when used
topically, these agents have a potent anti- used include lactic acid (a component of However, the cream was not superior to an
inammatory eect.11 natural moisturising factor) and glycolic acid. alternative containing urea. No other details of
One study with oatmeal extracts has shown One recent study in hairless mice showed that the cream were provided.16
a signicant reduction in irritation from repeated application of lactic acid 5 per cent
application of sodium lauryl sulphate, which or glycolic acid 5 per cent over 14 days did Hyaluronic acid
suggests a potential role for oatmeal products not change TEWL or capacitance but Hyaluronic acid is a glucosaminoglycan
in contact dermatitis.12 produced an increase in secretion of lamella (carbohydrate polymer) which is present in
bodies and a decrease in the number of several tissues in the body and is a well known
B vitamins stratum corneum layers, (ie, enhanced component of cartilage. This compound is
Pantothenic acid (vitamin B5) is a component desquamation) compared with the untreated often found in anti-ageing creams and some
of co-enzyme A that is essential to the normal group. Other studies have suggested that as commercial moisturisers. There do not appear
functioning of keratinocytes. There has been well as enhancing desquamation, the acids are to be any studies of hyaluronic acid as a
interest in nicotinamide, a vitamin B analogue, also incorporated into the lamella bodies and moisturiser but there is some evidence of a
because it has been shown to increase this leads to an increased ceramide synthesis role in epidermal hyperplasia, which occurs
ceramide synthesis and reduce TEWL in dry and a stronger barrier. after damage to the barrier with acetone.17
skin. It has also been shown that application There are several studies, some that are
signicantly reduced TEWL compared with randomised and double blind, using the alpha More recent products
petroleum jelly in atopic eczema.13 hydroxy acids in dry skin. In many studies, Studies on skin barrier recovery after
Dexpanthenol (the active ingredient in lactic acid is formulated as the sodium or treatment with acetone have shown that after
Bepanthen) is an alcoholic derivative of ammonium salt. In short, most suggest that application of a mixture of physiological
pantothenic acid and is often used as a lactic acid is an eective moisturising agent, lipids, those lipids were incorporated into
humectant. Used topically for seven days in a leading to improvements in skin hydration epidermal cells and processed for secretion in
randomised, double-blind placebo controlled although some also suggest that lactic acid the barrier repair process. It has been
study, dexpanthenol improved stratum based moisturisers are no more eective than suggested that the replacement of
corneum hydration and reduced TEWL.14 In simple occlusive agents such as lanolin. physiological lipids via moisturisers, might
a second randomised, double-blind study with improve atopic eczema.
patients who had atopic eczema, ichthyosis, Sodium pyrrolidone carboxylic acid In a recent study in mice models of
psoriasis or contact dermatitis, dexpanthanol Sodium pyrrolidone carboxylic acid (PCA) is inammation and atopic dermatitis, topical
(3 per cent) treatment for four weeks led to a a component of natural moisturising factor. It
greater than 80 per cent improvement in is formed from laggrin-derived free amino
symptom scores.15 acids. In the skin it is more likely to exist as the The author will be available to answer
ammonium salt. PCA is dramatically depleted questions on this topic until 2 May 2011
Alpha hydroxy acids in conditions such as psoriasis.
Alpha hydroxy acids are included in Although there are few clinical studies Ask the
moisturisers because they are thought to
facilitate desquamation, making them
particularly valuable in hyperkeratotic
demonstrating this agent improves xerotic
skin, one study has shown that a 5 per cent
sodium PCA cream improved hand dryness
expert
www.pjonline.com/ask-expert
disorders. The alpha hydroxy acids typically in women when used for up to six weeks.

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CPD

cent) for 30 days to normal increased the


Panel 2: evidence for moisturisers in eczema susceptibility to sodium lauryl sulphate30 and
nickel sulphate.31 These studies suggest that
dierences in moisturiser composition can
Studies with moisturisers have shown that it is possible to reduce the time to relapse in atopic potentially alter skin barrier function
eczema once the condition has been brought under control with the use of a topical corticosteroid. rendering the skin more sensitive to external
Grimalt et al showed, in a randomised trial with 173 children, that use of an emollient in moderate irritants. Whether or not such eects would
to severe atopic eczema for six weeks led to a significant improvement in SCORAD score and a occur in xerotic or diseased skin is unclear.
reduction in topical steroid use.33 In addition, Berth-Jones et al found that emollient use reduced However, a recent review has suggested that
the time to relapse requiring corticosteroid use to six weeks.34 moisturisers have an important role in the
In a study using methylprednisolone aceponate cream in patients with atopic eczema, Peserico management of psoriasis32 and the National
et al found that the probability of not experiencing a relapse when using only an emollient was 65.8 Institute for Health and Clinical Excellence
per cent after 16 weeks.35 Another study, of atopic eczema in children, found that using the vehicle has recommended that moisturisers should be
of tacrolimus (ie, an emollient) alone, the time to relapse was 38 days (compared with 173 days used daily in children with atopic eczema.
with tacrolimus) and there were no differences in quality of life scores between vehicle and active This conclusion seems to be based on a
treatments.36 consensus of clinical experience rather than
Finally, Cork et al found that increased patient education regarding the appropriate use of direct clinical evidence (see Panel 2).
moisturisers led to an 800 per cent increase in moisturiser use and a corresponding 89 per cent
reduction in the severity of the eczema.37 It is clear, therefore, that moisturisers have a potentially summary
valuable role to play in the management of atopic eczema. There is evidence that moisturisers can
relieve dryness induced by changes in
temperature and relative humidity or
associated with conditions such as eczema
and ichthyosis. It seems likely that glycerol
application of a ceramide-containing mixture stratum corneum and poorer barrier function and urea are probably eective hydrating
suppressed inammation. However, there is than other parts of the body as noted by agents although the data from clinical
only one published study on the use of topical higher TEWL. In addition, facial skin contains studies are ambiguous. Alpha hydroxy acids
ceramide mixtures in atopic eczema patients: a higher proportion of lipids, which are easily appear to have a noticeable eect on
Chamlin et al found that when children removed by washing with soap. The evidence desquamation and this is likely to be due to
substituted their usual moisturiser with a for ecacy for facial moisturisers is almost facilitation of corneodesmolysis. There is little
physiological ceramide mixture (other non-existent except for one study, which evidence to show superiority for any specic
therapies were continued), severity scores for showed that daily application of a moisturiser agent but such agents are likely to be of value
eczema improved signicantly.18 However, to the face in winter improved hydration and in hyperkeratotic skin conditions
although potentially eective in atopic reduced TEWL.27 Any moisturiser designed (eg, psoriasis).
eczema, a study using skin identical lipids for use on the face is normally a cream or There is a lack of suitable clinical studies to
compared with petroleum jelly in tape and lotion and will tend to be non-greasy and non- draw any rm conclusions regarding the wide
detergent stripped skin, found no dierence comedogenic. The shine observed with range of other chemical entities included in
between either preparation.19 greasy skin can be alleviated by the use of moisturisers but the evidence that is available,
The US Food and Drug Administration products containing agents, such as kaolin or appears to suggest that increased hydration
recently approved the products in Panel 1. talc, which absorb excess sebum. occurs when these agents are used.
There is no evidence from the literature to
selecting a moisturiser Benets and adverse eects recommend any particular preparation. It is
It has been estimated that the adherence rate With such scarce good quality evidence, up to the pharmaceutical and cosmetic
with topical treatment is between 55 and 66 readers may wonder if moisturisers are a industry to provide more clinical information
per cent.26 In eczema, moisturisers should be waste of time. Moreover, adverse eects (in based on patient studies if healthcare
applied as often as needed this could be six addition to allergies) have been reported and professionals are to be convinced that a
or seven times a day. It is important, therefore, some creams may worsen symptoms. Last specic formulation is superior to its
that patients are given adequate choice over year, it was found that aqueous cream competitors.
preparations because unacceptable products containing around 1 per cent sodium lauryl
are unlikely to be used. sulphate reduced the thickness of healthy skin
Patient factors that inuence choice are and increased its permeability to water loss
independent of clinical ecacy and include over four weeks.28 Sodium lauryl sulphate is
how the product feels on the skin, whether or able to reduce the stratum corneum thickness PRACTICE POINTS
not it is easily absorbed through the skin, and of normal skin signicantly following repeated
how it smells. Ideally, a moisturiser should also yet brief application. Although aqueous cream Reading is only one way to undertake CPD
be hypoallergenic and non-comedogenic. was originally designed to be used as a wash and the regulator will expect to see various
The market is split into products for facial product (hence with a short contact time), the approaches in a pharmacists CPD portfolio.
hand, foot or body use. The heaviness or cream is used by many patients as a cheap
thickness of a formulation relates to the leave-on emollient. A blanket restriction on 1 Target medicines use reviews at patients
amount of occlusive agents present and this creams containing sodium lauryl sulphate is with eczema or psoriasis this week.
can dictate how the product will be used. For unwise but aqueous cream should not be 2 With a colleague choose your top three
instance, night-time creams are often heavier. considered as a rst-line leave-on emollient. moisturisers, listing advantages and
A facial cream will typically consist of as much When used as a wash, it causes few problems. disadvantages.
as 80 per cent water, 5 per cent humectant The impact of long-term use of 3 Take time to ask patients for feedback on
(usually glycerin) and 4 per cent occlusives or moisturisers on normal skin has recently been products and use this to inform your
emollients. Moisturisers for body and hand studied and has shown some alarming adverse recommendations.
use will typically contain slightly more water eects such as an increase in TEWL, reduced
(85 per cent) and slightly less occlusives and capacitance (ie, greater dryness) as well as Consider making this activity one of your nine
emollients, although content can be as high as increased sensitivity to irritants.29 These CPD entries this year.
44 per cent. observations concur with some earlier work
The skin on the face receives the most demonstrating that application of a
exposure to the environment. It has a thinner moisturiser with a high lipid content (70 per

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11 Aries MF, Vaissiere C, Pinelli E, Pipy B, double-blind, randomized, vehicle-controlled Journal of Dermatology 2008;159:134856.
Charveron M. Avena Rhealba inhibits A23187- clinical study to evaluate the efficacy and 37 Cork MJ, Britton J, Butler L, Young S, Murphy
stimulated arachidonic acid mobilization, safety of MAS063DP (Atopiclair) in the R, Keohane SG. Comparison of parent
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inflammatory disorders. Biological & 2008;19:61925. and demonstration of topical therapies by a
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12 Vie K, Cours-Darne S, Vienne MP, Boyer F, Adjuvant treatment of atopic eczema: of Dermatology 2003;149:5829.
Dupuy P. Modulating effects of oatmeal assessment of an emollient containing N-
extracts in the sodium lauryl sulfate skin palmitoylethanolamine (ATOPA study). Journal CPD articles are commissioned by The
irritancy model. Skin Pharmacology and of the European Academy of Dermatology Pharmaceutical Journal and are not peer
Applied Skin Physiology 2002;15:1204. and Venereology. 2008;22:7382). reviewed.

April 2011
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