The fatty acids α-linolenic acid (ALA, C18:3 (n-3)) and linoleic acid (LA, C18:2 (n-6)) are essential in animals including humans, and therefore required in the diet. Deficiency of either fatty acid causes disease and death. Both fatty acids are converted through the same series of enzymes to a number of longer-chain polyunsaturated fatty acids that accumulate in cell membranes. These fatty acids are then metabolised by cells, where they function as signal molecules to control inflammatory and immune pathways. Because LA and ALA use the same enzyme system, high intake of one can decrease pathway flux for the other. Increasingly, research is showing that the low quality diet adopted by developed nations, consisting of refined carbohydrates and micronutrient poor processed foods, contains too much LA and too little ALA. The result is cell membrane ratios of n-6 to n-3 fatty acids that cause inflammation and disease.
Estimates suggest that the ratio of n-6 to n-3 fatty acids required for optimal health is ~3:1. However, current data puts the actual ratio at ~6 to 10:1. Consumption of n-3 fatty acids in the form of eicosapentanoic acid (EPA, C20:5 (n-3)) and docosahexanoic acid (DHA, C22:6 (n-3)) from fish oils have been shown to provide a number of health benefits because they restore the natural n-6 to n-3 fatty acids ratio in cell membranes. Current recommendations are to limit n-6 intakes from LA in polyunsaturated vegetable oils, and at the same time increase consumption of n-3 fatty acids from marine sources such as fatty fish or fish oil capsules. One condition that may benefit from such changes is cardiovascular disease. In particular, certain biomarkers for cardiovascular disease have been shown to improve upon fish oil supplementation in a growing body of research.
For example, researchers1 investigated the effects of 10 weeks of decreased n-6 to n-3 fatty acid intake in 17 healthy subjects. Fatty fish (3 times per week) in place of meat, which provided roughly 1.25 g/d EPA and DHA, was used to increase n-3 fatty acid intake. Avoidance of n-6 containing vegetable oils and their products, was also advised. Dietary records showed significant changes in the LA to ALA ratio at baseline (32.2) and following 10 weeks of intervention (2.2). Low density lipoprotein (LDL) plasma levels fell significantly during the intervention (2.5 to 2.3 mmol/L). Significant decreases in glucose oxidation (3.6 to 3.3 mg/kg.min) and increases in fatty acid oxidation (0.7 to 0.9 mg/kg.min) were also reported. The inflammatory marker tumour necrosis factor alpha (TNFα) decreased significantly, while adiponectin, a protein regulator of glucose and fatty acid oxidation increased significantly (6.5 to 7.6 µg/mL).
These results suggest that decreasing to the n-6 to n-3 ratio of the diet results favourable changes that might decrease the risk of cardiovascular disease. The increase in fatty acid oxidation and decrease in glucose oxidation suggest that fat loss may have occurred, and changes in body composition would have explained the changed in the cardiovascular biomarkers seen. For example, adiponectin plasma concentrations are associated inversely with body weight. Inflammation is also known to be inversely associated with body weight, and in this study TNFα was shown to decrease over 10 weeks. The 8 % improvement seen in LDL concentrations over the course of the study may have been explainable by a decrease in body weight. Fish oil supplementation is known to increase fatty acid oxidation and accelerate body fat loss. However, in this study body fat changes were not reported.