vidence suggests that some of the inconclusive results in nutritional intervention studies may be due to the presence of non-responders within the study population. For example, calcium is able to lower blood pressure in some individuals with hypertension, but a certain group of individuals are non-responders to this treatment (here). Genetic studies are confirming that study populations may include non-responders for other nutrients, and this sheds new light on results from intervention trials. Fish oil has recently been shown to affect human metabolism in a number of ways, and supplementation is recommended to reduce the risk of mortality associated with cardiovascular disease. However some data suggests that sub-groups of the population do not respond to fish oil supplements and this may relate to deletions of important genes coding for metabolising enzymes in the essential fatty acid pathways.
For example, one study1 investigated the effects of fish oil supplements in African Americans and then assessed the presence of a deletion in the arachidonate 5-lipoxegenase gene. The arachidonate 5-lipoxegenase enzyme initiates the first step in the production of leukotrienes such as the arachidonic acid (AA, C20:4 (n-6)) derived inflammatory leukotriene B4 and the eicosapentanoic acid (EPA, C20:5 (n-3)) derived anti-inflammatory leukotriene B5. The balance of these two leukotrienes contributes to the inflammatory status of the cell. The researchers found that fish oil supplementation increased the total n-3 fatty acid content and decreased the n-6 to n-3 fatty acid ratio of red blood cells in those subjects with at least one working copy of the arachidonate 5-lipoxegenase gene. Supplementation also increase high density lipoprotein (HDL) plasma concentrations. However, those with a double deletion did not respond to fish oil supplementation.
These results suggest that at least one working copy of the arachidonate 5-lipoxegenase gene is required in order to benefit from fish oil supplements with respect cardiovascular outcomes. This may explain some of the inconsistent results seen in intervention studies using fish oil supplements. This also emphasises the importance of selecting the correct study population in order to ensure that they are representative of the population of interest. Not surprisingly, individuals with two deleted copies of the arachidonate 5-lipoxegenase gene have an increased risk of cardiovascular disease, and from this study it appears that this might be due to an inability to metabolise dietary long chain fatty acids correctly. The authors also measured the effects of fish oil supplementation on the triglyceride concentrations of the subjects and found a 20 % reduction. This supports previous studies that show a significant beneficial effect of fish oil supplements of triglyceride concentrations.
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