The essential fatty acids (EFAs) linoleic acid (LA, C18:2 (n-6)) and α-linolenic acid (ALA, C18:3 (n-3)) can be metabolised to other more unsaturated, long-chain fatty acids by the insertion of additional double bonds during consecutive elongation and desaturation reactions. The ratios of the resulting fatty acids can have a profound effect on disease because EFA metabolites can form short-lived eicosanoid hormones that regulate inflammation. The primary site for polyunsaturated fatty acid metabolism is the liver, but can also occur in most other tissues. Dihomo-γ-linolenic (DGLA, C20:3 (n-6)) and arachidonic acid (AA, C20:4 (n-6) are metabolites of LA, and are converted to the anti-inflammatory series 1 or pro-inflammatory series 2 and 4 eicosanoids, respectively. Eicosapentanoic acid (EPA, C20:5 (n-3)) and docosahexanoic acid (DHA, C22:6 (n-3)) are metabolites of ALA and are converted to the anti-inflammatory series 3 eicosanoids.
Both ALA and LA are metabolised by the same set of elongase and desaturase enzymes (here). The EFAs from the n-3 and n-6 families therefore compete for enzymes, with both delta-5-desatuse and delta-6-desturase exhibiting preference for the n-3 fatty acids provided that the dietary ratio is less than 4:1 (n-6:n-3). Traditionally the n-6 to n-3 ratio was around 4:1 in the human ancestral diet, but the Western diet has altered this ratio to between 10:1 to 20:1 by a combination of increased LA consumption and decreased ALA consumption. Excess LA is converted to AA, which accumulates in cell membranes. The enzymes cyclooxygenase (COX) and lipoxygenase (LOX) can convert AA to the series 2 prostaglandins and thromboxanes as well as the series 4 leukotrienes. These eicosanoids have been shown to be involved in the development of cardiovascular disease, obesity, cancer, arthritis and Alzheimer’s disease.
A solution to the inflammation caused by high LA intakes is to increase consumption of ALA from sources such as flax seeds and hemp. Walnuts are a rich source of ALA, but also contain roughly five times as much LA and so do not redress the imbalance. However, conversion of ALA to EPA and DHA in humans is not efficient and research investigating the anti-inflammatory effects of ALA have produced mixed results. A better solution is to supplement the diet with EPA and DHA directly. Increasing consumption of these marine long-chain fatty acids results in AA being partially displaced from the cell membranes decreasing the production of pro-inflammatory eicosanoids. In additions, EPA and DHA are able to inhibit inflammation by competition for the 5-lipoxygenase enzyme necessary for AA derived pro-inflammatory mediators. Numerous studies have shown that supplementation with EPA and DHA has a significant effect to reduce inflammation.
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