The essential fatty acids α-linolenic acid (ALA, C18 (n-3)) and linoleic acid (LA, C18:2 (n-6)) play an important role in the formation of eicosanoids. Eicosanoids are 20-carbon chemicals that act as local hormones to regulate cellular inflammation. Eicosanoids can be subcategorised into the leukotrienes, thromboxanes and prostaglandins. Three metabolites of the essential fatty acids lead to the formation of three distinct groups of eicosanoids and the ratio of these metabolites in cell membranes determines the inflammatory state of the cell. Dihomo-γ-linolenic acid (DGLA, C20:3 (n-6)) is a metabolite of linoleic acid and lead to the formation of the anti-inflammatory series 1 prostaglandin PGE1. Arachidonic acid (AA, C20:4 (n-6)) is also a metabolite of LA and leads to the formation of the pro-inflammatory series 2 prostaglandins and the series 4 leukotrienes. Eicosapentanoic acid (EPA, C20:5 (n-3)) is a metabolite of ALA and leads to the formation of the mildly anti-inflammatory series 3 prostaglandins and series 5 leukotrienes.
Altering the composition of polyunsaturated fatty acids in the diet can influence inflammation because the ratios of the precursor molecules to the eicosanoids (EPA, AA and DGLA) in the cell membranes is dependent on the dietary intake of LA and ALA, as well as EPA, DGLA and AA. Increased consumption of ALA, EPA and DGLA tends to be anti-inflammatory whereas increased consumption of LA (if excessive) and AA tends to be pro-inflammatory. Although DGLA is needed for the synthesis of PGE1, dietary sources of this long chain fatty acid are rare. However, γ-linolenic acid (GLA, C18:3 (n-6)) is founding high concentrations in both starflower oil (borage oil) and evening primrose oil (EPA) and research has shown both to be beneficial at treating inflammatory conditions when given as supplements. This is because GLA causes increases in DGLA in cell membranes, which in turn is converted to PGE1. GLA has pronounced anti-inflammatory effects of certain skin and rheumatic condition.
Like all prostaglandins PGE1 has the potential to cause pro-inflammatory conditions in cells. However, the action of PGE1 in inflammatory cells such as leukocytes is overwhelmingly inhibitory. Prostaglandin E1 therefore has a general anti-inflammatory effect which is thought to occur for a number of reasons. Firstly, PGE1 causes the release of cellular cyclic AMP (cAMP) which inhibits the release of a number of substances that cause inflammation such as lysosomal enzymes. Increased cAMP also reduces chemotaxis and reduces the adhesive properties of the cells. The conversion of GLA to DGLA also increases production of 15-hydroxyl derivatives of leukotrienes that may inhibit the formation of inflammatory series 4 leukotrienes from arachidonic acid. The conversion of DGLA to PGE1 also uses the same cyclooxygenase enzyme that is needed by arachidonic acid to form the series 2 prostaglandins and so increased production of PGE1 reduces the production of the pro0inflammatory series 2 prostaglandins.
The effects of GLA on rheumatoid arthritis has been extensively studied but many of the studies contain inappropriate study design. For example, many placebo controlled trials have used olive oil as the placebo. However, olive oil may have anti-inflammatory effect itself and so it in these trials GLA tended not to show improvements over the placebo. To address this problem other researchers1 have used liquid paraffin as a placebo because of its inert effects metabolically. In these trials, 12 months of supplementation with 540 mg of GLA in 12 EPO capsules or 450 mg GLA and 240 mg EPA in the form of an EPO-fish oil mix resulted in the subjects requiring fewer nonsteroidal anti-inflammatory medicine to control the pain from their arthritis. From these results and others using appropriate placebos, GLA appears to have beneficial effects on certain conditions characterised by inflammation.
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