IT is about 20 years since essential
fatty acids were first widely
advocated in veterinary
dermatology and their introduction
was consolidated in the veterinary
literature by a whole issue of
Veterinary Dermatology dedicated
to understanding their role and
usefulness in dogs and cats.1
Since then our knowledge of the
structure and function of
the skin has
increased,
indicating
that the role
of lipids in
the skin is
crucial to our
interpretation and treatment of
dermatological disease.
Sources of essential fatty
acids
There are two families of
polyunsaturated fatty acids (pFAs).
The n-6 fatty acids are derived from
linoleic acid (18:2n-6) and are widely
found in vegetables and seed oils such
as sunflower or evening primrose.
The n-3 fatty acids are derived
from alpha-linolenic acid (18:3n-3),
which are found in green leafy
vegetables. An important metabolite
of alpha-linolenic acid,
eicosapentaenoic acid (20:5n-3) is
found in fish oils.
Both families of pFAs are
metabolised by the same pathway of
enzymes, which act to desaturate and
elongate fatty acid molecules.
However, animals cannot convert n-3
to n-6 fatty acids. The epidermis is
not equipped with 5-desaturase or 6-
desaturase enzymes and most
metabolism occurs in the liver.
Linoleic and α-linolenic acids are
considered essential in dogs and cats
with dietary arachidonic acid also
being essential in the cat (see Figure
1).
The functions of epidermal
lipids
Epidermal lipids are important in four main functions of the skin.2 The most
important is barrier function, but after
this comes moisturisation of the
stratum corneum, cohesion and
desquamation of keratinocytes and
influences upon epidermal
proliferation and differentiation.
The skin is present to act as a
barrier and the combination of
keratin proteins, tight intercellular junctions and the terminal
differentiation of the keratinocyte to
form the corneocyte is the
foundation for this protection.
However, without the lipid that fills
the spaces between cells, this
protection fails.
Lipid is not squeezed between the
corneocytes in a random fashion, but
the combination of fatty acids,
cholesterol, and ceramides is highly
organised to form sheets (lipid
lamellae) with a defined structure3
and it is the quality of these lipids
that determine the permeability of
the epidermis.4
The water holding capacity of the
skin, measured by transepidermal
water loss (TEWL), has been
described by several authors.5-8
In disease, skin water is lost from
the skin at an increased rate and
TEWL is increased. In healthy skin,
this is prevented by lipids in the
stratum corneum facilitated by amino
acids formed by the breakdown of
filaggrin (e.g. histadine).
In atopic dermatitis the lipid lamellae are seen to be disrupted9 and
TEWL is also increased.6,7,10 However,
whereas in man where TEWL is a
useful marker of disease severity, this
is not so in dogs.11
Desquamation is an essential part
of skin defence. Corneocytes are
shed into the environment carrying
away bacteria, yeasts and other
contaminants. Cutaneous lipid
abnormalities usually result in scale
building up on the skin surface, called
retention hyperkeratosis.12
The control of epidermal
proliferation and differentiation is
highly complex and reflects local
environmental effectors and systemic
effectors such as hormones. Locally,
an inadequate lipid barrier may
directly, or indirectly through
secondary infection, change the rate
of turnover of skin cells and the
maturation process.
Eisconanoids produced through
the metabolism of fatty acids often
cause epidermal hyperplasia and an
increased epidermal turnover2, but
may cause a reduction in barrier
function through reduced
development of corneocytes.13
Eicosanoids are derived from
fatty acid precursors and have pro-
inflammatory and anti-inflammatory
actions. The 1-series prostaglandins
and thromboxanes are derived from
di-homo-γ-linolenic acid, the 5-series
leukotrienes and 3-series
prostaglandins and thromboxanes are
derived from eicosapentanoic acid
and a vast array of eicosanoids
including the 2-series prostaglandins
(e.g. PGD2, PGE2) and thromboxane
via cyclo-oxygenase, leukotrienes
such as LTB4 (via 5 lipoxygenase) as
well as products of 12- and 15-
lipoxygenase such as 12-HETE and
15-HETE.
When arachidonic acid is
released from the cell wall it
is converted immediately
into various eicosanoids, the
nature of which is
determined by the nature of
the stimulus, the cell type
and the
maturation/differentiation of
the cell.
As there are long
pathways involved in the
conversion of essential fatty
acids into their active
metabolites, there is potential
to reduce the production of
pro-inflammatory
eicosanoids in favour of
anti-inflammatory
metabolites through
supplementation with fatty
acids, particularly di-homo-γ-linolenic acid (GLA) and
eicosapentaenoic acid (EPA).
EFAs in canine dermatology
Good quality dog foods should
contain sufficient levels of linoleic
acid for normal dogs and cats.
However, even in these normal
animals, EFA supplementation will
often result in an improvement in
coat quality and gloss with an
associated reduction of
transepidermal water loss (TEWL).14
Where there is seborrhoea sicca,
the cutaneous levels of linoleic acid
are low and supplementation will
restore the levels.15 Excessive cooking
may reduce linoleic acid in foods that
would otherwise have acceptable
levels. Many dogs with scaling skin
disease will benefit from EFA
supplementation, and EFAs are
widely used in idiopathic scaling and
sebaceous adenitis.
EFA supplementation is
considered to be useful in ichthyosis
of the golden retriever by this
author16, and is used in combination
with baths.
Many clients report an
improvement in this scaling condition
caused by a mutation in the PNPLA1
gene that has a key role in the lipid
organisation and metabolism of the
epidermal barrier.17 However, others
have reported poor results with EFA
supplementation in a small number
of cases.18
The use of EFA supplementation
for atopic dermatitis and other
inflammatory skin diseases in the dog and cat has been the focus of
research attention for some time19,20;
however, there is still considerable
confusion regarding their use.
Although widely used, questions that
remain to be answered include the
optimum dose, optimum ratio of n-
3:n-6 fatty acids and their efficacy.
A number of studies suggest that
EFAs are helpful in reducing pruritus
or erythema, without undue adverse
effects19-22, and in one study the
treatment combining shampoo and
EFA supplementation was compared
favourably to the use of
prednisolone23, which is a higher level
of efficacy than generally reported.
However, many studies suffer
from the lack of a standardisation.
Importantly, a standardised diet was
not used during many of the trials.
This may lead to the wide variation in
the EFAs being fed and have a great
influence on the results.
Other trials, some as short as two
weeks in duration, are too short to
allow this food supplement to have
maximum effect. Also, a wide variety
of products containing EFAs have
been tested, including evening
primrose oil or borage oil, with or
without additional constituents, such
as fish oils.
This has resulted in a lack of
consensus as to the correct ratio of
n-6:n-3 fatty acids and a clear
indication of the efficacy of these
apparently useful products.
A recent trial addressed the issue
of consistency of the diet24 and
suggested that dogs with early atopic
disease might be more successfully
managed using EFA
supplementation, but did not
continue the trial for the three
months recommended by Olivry and
colleagues.25
A more recent review26 looked
critically at the body of work
available and considered two studies
to be well-designed and clear
evidence for a steroid-sparing effect
when using EFAs.27
EFAs in feline dermatology
EFA supplements have been
recommended for use in allergic,
pruritic disorders in the cat. There
are marked differences in the
biochemistry of the lipids in the cat
as they have no 6-desaturase activity.
This means that di-homo-γ-
linolenic acid or arachidonic acid as
well as linolenic acid are needed for
n-6 fatty acid metabolism. An
alternative pathway circumventing the
6-desaturase pathway is suspected,
but a diet of 18:2n6 fatty acid will
not ameliorate all the cutaneous signs
of fatty acid deficiency.
EFAs have been recommended
for papulocrusting dermatoses (flea
bite hypersensitivity, atopic dermatitis and idiopathic disease).28 A reduced
efficacy was noted when n-3 fatty
acids were used alone compared to
either n-6 fatty acids or a mixture of
n-6 and n-3 fatty acids.29 In light of
this, tuna and other fish oils may not
be beneficial to cats with skin disease.
Adverse effects
Adverse effects of EFA
administration have been rarely
reported. Perhaps the most serious
potential side effect is pancreatitis.
Soft stool and contribution to obesity
are more common.
Concern that n-3 EFAs may
contribute to bleeding disorders and
platelet abnormalities have not been
supported30 and similarly a recent
trial, albeit rather short in duration,
does not suggest that EFAs lower the
threshold for seizures in epilepsy.31
Recommendations
The role of fatty acids in a healthy
skin is clear, but there is still
considerable work to be done to
hone our knowledge to use these
agents effectively. Dogs and cats
given EFA supplementation will show
beneficial coat changes and may show
reduced need for more potent
medications to control their
inflammatory skin disease.
The low rate of adverse effects
makes EFA supplements an ideal
treatment for milder cases of atopic
dermatitis and as an adjuvant
treatment in more severe cases.
1. Lloyd, D. H. (1993) Veterinary Uses of
Essential Fatty Acids. Vet Dermatol 4 (4):
iii.
2. Kwochka, K. W. (1993) The structure
and function of epidermal lipids. Vet
Dermatol 4 (4): 151-159.
3. Elias, P. M. (1983) Epidermal Lipids,
Barrier Function, and Desquamation. J
Invest Dermatol 80 (6 Supplement): 44s-
49s.
4. Elias, P. M. et al (1981) Percutaneous
transport in relation to stratum corneum
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Dermatol 76 (4): 297-301.
5. Lau-Gillard, P. J. et al. (2010)
Evaluation of a hand-held evaporimeter
(VapoMeter) for the measurement of
transepidermal water loss in healthy dogs.
Vet Dermatol 21 (2): 136-145.
6. Hightower, K., Marsella, R. and Flynn-
Lurie, A. (2010) Effects of age and
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7. Shimada, K. et al (2009) Increased
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8. Shimada, K. et al (2008)
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normal and atopic dogs. Vet
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10. Cornegliani, L. et al (2012)
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11. Marsella, R. (2012) Are
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18. Cadiergues, M. C. et al (2008)
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