Consumption of fructose is associated with an increase in serum triglyceride levels, a known risk factor for cardiovascular disease, as well as elevated levels of serum free fatty acids (FFA). Elevated triglycerides and FFA may lead to lipid accumulation in skeletal muscle, which is able to cause insulin resistance due to interference with normal lipid signal molecules that are required for the insulin signal cascade. In turn, insulin dysfunction may then result in a reduced nitric oxide synthesis in the vascular endothelium, which results in impaired peripheral dilation. Nitric oxide is also required to inhibit platelet aggregation and monocyte adherence in cell walls, and so high triglyceride and FFA concentrations may lead to atherosclerotic plaque formation. Fish oils show promise as cardioprotective agents, and this may in part be due to their ability to reverse vascular dysfunction associated with raised triglyceride and FFA concentrations.
Research1 investigating the effects of docosahexanoic acid (DHA, C22:6 (n-3)) from fish oil on the vascular dysfunction caused by elevated concentrations on non-esterified fatty acids found a benefit to flow mediated dilation (FMD). In the study, 59 subjects were given a repeated oral fat feeding of either palmitic acid or palmitic acid with DHA on two separate occasion, along with a heparin infusion to elevate non-esterified fatty acid concentrations for between 60 and 240 min. This methodology was designed to simulate the elevated FFA that might be associated with insulin resistance. The elevation in FFA was associated with impairment of the FMD of the brachial artery. However a positive association was found between the concentration of n-3 long chain fatty acids in circulation and the flow mediated dilation of the brachial artery, suggesting that DHA supplementation was beneficial to vascular function.
The 3 to 5-fold increase in the levels of long chain n-3 fatty acids that was able to reverse the detrimental changes to FMD comprised of eicosapentanoic acid (EPA, C20:5 (n-3)) as well as DHA. This is because DHA is metabolised to EPA via elongase and desaturase enzymes during normal metabolism. Supplemental EPA may therefore have had a similar beneficial effect on FMD. This supports data from other researchers which also shows positive dilation effects with 0.9g of EPA and DHA. However, paradoxically, DHA and EPA causes the same reduction in nitric oxide seen with elevate levels of saturated FFA suggesting that the benefits to dilation are not caused by elevations of nitric oxide synthesis. Instead, some evidence suggests that cytochrome P450 (epoxygenase) enzymes can metabolise long chain fatty acids to epoxides which may have dilatory effects in the endothelium of blood vessels.
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