yclooxygenase (COX) inhibitors are a sub-group of the non-steroidal anti-inflammatory drugs. These drugs, that include common over the counter medicines such as aspirin and ibuprofen, inhibit the cyclooxygenase enzymes non-selectively. Cyclooxygenases are a group of enzymes required for eicosanoid (prostanoid) synthesis. In this role, cyclooxygenase converts long chain fatty acids such as arachidonic acid (AA, C20:4 (n-6)), eicosapentanoic acid (EPA, C20:5 (n-3)) and dihomo-γ-linolenic acid (DGLA, C20:3 (n-6)) to prostaglandins, prostacyclins and thromboxanes of series 2, 3 and 1, respectively. Series 2 eicosanoids are pro-inflammatory, cause blood vessel constriction and platelet aggregation, and can lead to sodium retention in the kidney. In contrast, series 1 eicosanoids are anti-inflammatory, prevent platelet aggregation, dilate blood vessels and cause excretion of sodium. Series 3 eicosanoids are neutral in nature, but because their synthesis involves activation of cyclooxygenase, they antagonise the effects of series 2 eicosanoids.
Therefore consumption of fish oil reduces cardiovascular disease risk because it contains EPA, which can be converted to series 3 eicosanoids that inhibits the synthesis of pro-inflammatory series 2 eicosanoids that cause blood pressure rises and platelet aggregation. Consumption of plant oils containing precursors of DGLA, such as γ-linolenic acid (GLA, C18:3 (n-6)), can also decrease cardiovascular risk because their eicosanoid products have strong anti-inflammatory, blood pressure lowering and anti-platelet effects. Consumption of plant and fish oils therefore explains many of the health benefits associated with high quality diets with regard cardiovascular disease. Poor quality diets high in red meat, sugar and trans fatty acids, as well as stress, are particularly problematic at stimulating series 2 eicosanoid formation. Disease and inflammation results when the cellular production of series 2 eicosanoids becomes excessive and dominates the cyclooxygenase enzyme system, inhibiting the beneficial series 1 and 3 eicosanoids.
When conditions favour the production of the pro-inflammatory, platelet aggregatory, blood pressure rising series 2 eicosanoids, cyclooxygenase inhibitors such as aspirin and ibuprofen can be beneficial. Under these circumstances, short-term inhibition of all cyclooxygenase activity is more beneficial when compared to allowing conditions of excessive series 2 production (caused by poor diet). However, while they produce favourable short-term effects during pro-inflammatory states, long term intakes result in deteriorating cardiac health because as well as inhibiting production of the unfavourable eicosanoids, they also inhibit production of the eicosanoids that are beneficial to health. This ‘reverse fish oil effect’ explains the 3-fold increase in the risk of stroke as well as the increased risk of haemorrhagic strokes with long-term consumption of ibuprofen1 and aspirin2, respectively. Plant and fish oils are effective long-term treatments for cardiovascular disease, because they decrease damaging series 1 eicosanoids and increase beneficial series 1 and 3 eicosanoids.
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