Consumption of oily fish and
fish oils is associated with protection against
cardiovascular disease. Paradoxically, long-chain
polyunsaturated fatty acids present in
low-density lipoprotein (
LDL) are suggested to be susceptible to oxidation. It is not clear whether
eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA) have similar effects on the susceptibility of
LDL to oxidation or whether they affect the thrombogenicity of
oxidized LDL. This study examined the influence of highly purified preparations of EPA and DHA on
LDL oxidizability and
LDL-supported
thrombin generation in healthy human volunteers. Forty-two healthy volunteers were randomly assigned to receive
olive oil (placebo), an EPA-rich oil or a DHA-rich oil for 4 weeks at a dose of 9 g oil/day. EPA and DHA were incorporated into
LDL phospholipids and
cholesteryl esters during the supplementation period, but were progressively lost during ex vivo
copper-mediated oxidation. Following supplementation, the EPA treatment significantly increased the formation of conjugated dienes during
LDL oxidation compared with baseline, whereas the DHA treatment had no effect. Neither treatment significantly affected the lag time for oxidation, oxidation rate during the propagation phase or maximum diene production. Neither EPA nor DHA significantly affected the thrombotic tendency of
oxidized LDL compared with the placebo, although DHA tended to decrease it. In conclusion, there are subtle differences in the effects of EPA and DHA on the oxidizability and thrombogenicity of
LDL. DHA does not appear to increase the susceptibility of
LDL to oxidation to the same degree as EPA and has a tendency to decrease
LDL-supported
thrombin generation.