Skin conditions are associated with n-6 fatty acids but generally not with n-3 fatty acid. The result of n-6 deficiency is increased inflammation, which includes heat, pain, redness, swelling, and loss of function. This can cause weeping, increased proliferation of epidermal cells, increased permeability to water, increased metabolic activity, abnormal keratinocytes and an increase in the formation of sterol esters. It was originally thought that atopic dermatitis (eczema) was caused by low levels of essential fatty acids in the skin, because the condition responded well to high levels of LA (LA, C18:3 (n-6)). However, it is now known that LA is present in skin in high concentrations in cases of atopic dermatitis. Instead there are low levels of LA metabolites γ-linolenic acid (GLA, 18:3 (n-6)), dihomo- γ-linolenic (DGLA, 20:3 (n-6), arachidonic acid (AA, 20: 4 (n-6)), Adrenic acid (ADA, 22:4 (n-6)) and docosapentanoic acid (DPA, 22:5 (n-6)).
These high levels of LA, but low levels of metabolites in cases of atopic dermatitis suggests that there is an impaired conversion of LA to its metabolites. Levels of alpha linolenic acid (ALA, C:18 (n-3)) are also elevated and concentrations of its metabolites are reduced, indicating a common enzyme deficiency. Evidence suggests that reduced Δ6-desaturase enzyme activity may be present in atopic dermatitis. This might be because of altered expression of the gene, changes in co-factors required for the enzyme, a change in hormonal regulation or the presence of enzyme inhibitors. The end result is a reduced rate of conversion of LA to its metabolites, and perhaps a reduced incorporation of EFAs into phospholipids, both of which leads to reduced formation of prostaglandin E1 (PGE1). This in turn lowers concentrations of cyclic AMP and as a result makes the immune system hypersensitive.
If atopic dermatitis is caused by a reduced conversion of LA to GLA because of Δ6-desaturase deficiency, then it would be expected that GLA supplementation would alleviate the condition. A number of studies in patients with atopic dermatitis have successfully used evening primrose oil, which contains ≈72% LA and ≈9% GLA, to produce a dose-related rise in plasma phospholipid DGLA. Increases in the levels of DGLA may contribute to an anti-inflammatory and proliferation controlling effect through two mechanisms. Firstly, DGLA can be metabolised to the anti-inflammatory series 1 prostaglandins, particularly PGE1 which can stimulate cyclic AMP and inhibit phospholipase. Secondly, DGLA can be metabolised to 15-hydroxy-DGLA, which can inhibit the enzyme lipoxygenase and subsequently reduce the formation of the pro-inflammatory leukotrienes. Meta-analysis of placebo controlled trials indicates that there is a significant improvement in atopic dermatitis with evening primrose oil supplementation. .
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