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Essential fatty acids revisited

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01 June 2008, at 12:00am

SUE PATERSON traces the history and asks which supplement is best

ALTHOUGH essential fatty acids were discovered in the late 1920s, their true medicinal potential lay undiscovered until after the second world war, in the early 1950s, when the work of a group of researchers from Oxford, including a man called David Horrobin, was published.

These workers produced a scientific rationale indicating that Gamma Linolenic Acid (GLA) derived from the seeds of the evening primrose oil plant could be beneficially linked to the quality of human health and nutrition.

David Horrobin famously went on to found Efamol Ltd in 1977 and later, in 1981, he established The Efamol Research Institute. Efamol quickly became and still is a pioneer in the research and development of essential fatty acid supplements.

The first essential fatty acid supplement, Efamol pure evening primrose oil, was produced in 1978 and soon became a brand leader in both human and veterinary medicine. However, since Efamol’s initial success the market has seen an explosion in the number and range of essential fatty acid (EFA) supplements that have become available.

They have been produced in a wide variety of formulations and in addition to the original oil capsule now produced amongst others as Coatex and Viacutin, they are available as pump-action liquid spray as Viacutin and also now for dogs as a carob-based chocolate rich in EFAs called Boracutin.

The first veterinary report proposing EFAs as a therapy for canine atopic dermatitis was published in 1987 by Pukay. This was swiftly followed by a rash of further studies from workers in the States and the UK. Initial studies were open trials aimed almost as a taster to see if EFAs, which at the time were demonstrating enormous potential benefits in human medicine, held the same prospects for the veterinary profession. Retrospective analysis of much of this early work reveals its limitations and shows some of it to be critically flawed. Many of the studies were short lasting, little more than two weeks, which was barely sufficient time for any judgment to be made on a supplement. EFAs were given as symptomatic therapy for dogs where a definitive diagnosis had not been made. Often investigations were not placebo controlled or blinded, both important prerequisites for a meaningful study.

As a result of these deficiencies, some study results should be interpreted with caution. However, despite the fact that early promise was never fully realised, there is no doubt that EFA supplementation has some benefits for allergic individuals.

When faced with a decision on prescription, though, the contentious questions remains: which EFA supplement is the best? With the wide range of supplements and the different mixes of omega 3 and omega 6 oils that are available, there is much confusion as to the importance of the different components and what should be the optimum concentration of each of the oils.

EFAs appear to wear two hats in their anti-allergic role. It is well recognised that they exhibit a range of anti-inflammatory and immunomodulating properties but they also possess the ability to improve the quality of epidermal lipids.

Work by Karen Campbell has shown that oil supplementation can increase cutaneous fatty acid concentrations and significantly decrease transepidermal water loss. It is this second factor that seems to be particularly interesting in the light of recent research on the aetiopathogen-esis of atopic eczema in man.

The anti-inflammatory effects of EFAs

The anti-inflammatory effect of EFAs is mediated by their ability to modulate the cutaneous production of prostaglandins and leukotrienes. The omega 6 essential fatty acids that are high in GLA are thought to increase dihomo-gamma linolenic acid (DGLA) production and subsequent degradation which leads to an increase in anti-inflammatory mediators at the expense of arachidonic acid (AA). Omega 3 EFAs also appear to be able to alter the metabolism of AA derived inflammatory mediators.

Eicosapentaenoic acid (EPA) also competes with AA and favours the production of anti-inflammatory mediators. The ratio of omega 6:omega 3 EFAs that is optimally beneficial still remains a subject of some debate; however, work by Vaughn suggested diets with a ratio of omega 6:omega 3 of 5:1 and 10:1 ratio resulted in decreased production of pro-inflammatory leukotrienes and an increased production of anti-inflammatory leukotrienes in dogs’ skin.

The hydrating effects of EFAs

Recent ground-breaking work in human medicine has identified specific genetic mutations in people with atopic dermatitis. One of the most interesting findings is a mutation in the gene encoding for filaggrin.

Filaggrin is known to be important in barrier function in the skin. It is formed from pro-filaggrin within keratohyline granules in the granular cell layer of the epidermis (Figure 1).

Filaggrin is the matrix protein that is important in binding the keratin filaments together and anchoring them to the cell envelope. Once the filaments are tightly packed to form the dense superstructure required in the corneocytes of the stratum corneum, the filaggrin is digested by proteases to free amino acids that help maintain the water binding characteristics of the horny layer.

Without adequate levels of filaggrin and its degradation products in the epidermis, an increase in transepidermal water loss occurs, leading to dryness of the skin. These changes may lead to an increased penetration of antigens into the skin and subsequent binding to IgE on the surface of antigen presenting cells such as Langerhans cells.

Interestingly, similar faults in filaggrin formation have been identified in ichthyosis vulgaris, the most common form of ichthyosis, a keratinisation disorder, in man. Levels of dihomogamma-linolenic acid derived from GLA have also been shown to be low in ichthyosis vulgaris.

Therapy of ichthyosis has long been directed at improving skin hydration with emollients and moisturisers, especially products high in alpha hydroxy acids and certainly supplementation with essential fatty acids, especially those high in GLA, are justified in the light of experimental findings.

In atopic dermatitis in man there is also a move away from more and more potent anti-inflammatory drugs towards improved skin care. The regular use of emollients and skin hydration is mandatory to improve dryness which helps control pruritus.

The identification of specific faults in the canine atopic skin is not as advanced as in man. However, in dogs, abnormalities in EFAs contributing to the skin barrier and in the intercellular lipid lamellae have been identified and there is no doubt many dogs with atopy have dry scaly skin (Figure 2).

Electron microscopic observations by Inman and co-workers have identified a wide range of abnormalities in the skin of atopic dogs. One striking finding was that the intercellular lipid lamellae in the stratum corneum of atopic dogs have many structural defects, suggesting that an epidermal barrier defect may be present.

Selecting EFAs for therapy

In the author’s experience, EFAs produce only a moderate improvement in their ability to control pruritus through their direct anti-inflammatory effect in dogs with atopic disease. They have been shown to be synergistic when used with antihistamines and have been shown to have good steroid sparing effects when used in combination with glucocorticoids to control clinical signs in atopic dogs.

Logically, however, it would seem they hold the most potential when used long term with topical emollients to improve skin condition. As to whether omega 3 or omega 6 essential fatty acids should be used, the research would suggest that it is GLA, an omega 6 fatty acid, that is most important as a precursor of DGLA in improvement in skin quality and probably omega 3 fatty acids may have more anti-inflammatory effects.

As to the concentrations of each component, this has yet to be definitely reported. In deciding on dose rate of GLA, the author’s opinion is that the higher the levels of administered GLA (without, of course, inducing gastrointestinal side effects) the better, in order to maximise benefit for skin improvement. Also supplementation for atopic dogs should be life-long to try to counteract pre-existing cutaneous abnormalities.

Further reading

Bond. R. and Lloyd, D. H. (1994) Combined treatment with concentrated essential fatty acids and prednisolone in the management of canine atopy. Vet Rec. 134: 30-32.

Campbell, K. L., Czarnecki-Maulden, G. L. and Schaeffer, D. J. Effects of animal and soy fats and proteins in the diet on fatty acid concentrations in the serum and skin of dogs. Am. J. Vet. Res. 56: 1,465-1,469.

Grattan, C., Burton, J. L., Manku, M., Stewart, C. and Horrobin, D. F. (1990) Essential-fatty-acid metabolites in plasma phospholipids in patients with ichthyosis vulgaris, acne vulgaris and psoriasis. Clin Exp Dermatol. 15 (3): 174-176.

Inman, A. O., Olivry, T., Dunston, S. M., Monteiro-Riviere, N. A. and Gatto, H. (2001) Electron microscopic observations of stratum corneum intercellular lipids in normal and atopic dogs. Vet Pathol. 38: 720-723.

Macheleidt, O., Kaiser, H. W. and Sandhoff, K. (2002) Deficiency of epidermal protein-bound omegahydroxyceramides in atopic dermatitis. J Invest Dermatol. 119: 166-173.

Olivry, T. and Hill, P. B. (2001) The ACVD Taskforce on canine atopic dermatitis: (VIII) is the epidermal lipid barrier defective Vet Immunol Immunopathol. 81: 215-218.

Palmer, C. N., Irvine, A. D., TerronKwiatkowski, A., et al. (2006) Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 38: 441-446.

Paterson, S. (1996) Additive benefits of EFAs in dogs with atopic dermatitis after partial response to antihistamine therapy. J. Sm. Anim. Pract. 36: 389-394.

Pukay, B. A. (1987) Clinical evaluation of the efficacy of omega 3 fatty acids in the treatment of pruritus in canine atopy. CAVD Bull 4: 2-4.

Werner, Y. and Lindberg, M. (1985) Transepidermal water loss in dry and clinically normal skin in patients with atopic dermatitis. Acta Derm Venereol 65: 102-105.