hyperpolarization and relaxation of vascular smooth muscle cells. 13 Importantly, because the production of AA from LA is tightly regulated, 14 wide variations in dietary LA (above minimal essential intakes) do not materially alter tissue AA content. 15 In tracer studies, the extent of conversion of LA to AA is 0.2%. 16

In studies with vascular endothelial cells, omega-6 PUFA had antiinflammatory properties, suppressing the production of adhesion molecules, chemokines, and interleukins, all key mediators of the atherosclerotic process. 17 In human studies, higher plasma levels of omega-6 PUFAs, mainly AA, were associated with decreased plasma levels of serum proinflammatory markers, particularly interleukin-6 and interleukin-1 receptor antagonist, and increased levels of antiinflammatory markers, particularly transforming growth factor-. 18 When healthy volunteers were given 7 times the usual intake of AA (ie, 1.5 g/d) in a 7-week controlled feeding study, no effects on platelet aggregation, bleeding times, the balance of vasoactive metabolites, serum lipid levels, or immune response were observed. 5–8 Likewise, in a recent study from Japan, AA supplementation (840 mg/d for 4 weeks) had no effect on any metabolic parameter or platelet function. 19 Consistent with this, in observational studies, higher omega-6 PUFA consumption was associated with unaltered or lower levels of inflammatory markers. 20 Diets high in LA can increase the ex vivo susceptibility of low-density lipoprotein (LDL) to oxidation, 21 and oxidized LDL can promote vascular inflammation. 22 Therefore, oxidized LDL may play some role in the etiology of CHD. 23 However, the extent of LDL oxidation at higher LA intakes (5% to 15% of energy) has not been established, and its clinical relevance is in question owing to the general failure of antioxidant treatments to mitigate CHD risk in most randomized trials. 24 At present, little direct evidence supports a net proinflammatory, proatherogenic effect of LA in