Assessment of the Therapeutic Use of Dietary Fish Oil in Atherosclerotic Vascular Disease and Thrombosis: Blood Vessels and Coagulation Factors

17 Oct

Effects of Fish Oil on Platelets, Blood Vessels and Coagulation Factors
When fish oils are fed to humans, substantial amounts of the omega-3 polyunsaturated fatty acids, EPA and DHA, accumulate in platelet membrane phospholipids. In one study, the platelet content of EPA rose from negligible amounts to 6.1% and DHA increased from 1.1% to 3.7% after fish oil feeding. In contrast, there was a fall in platelet arachidonic acid from 28% to 20%. When highly purified omega-3 fatty acids as ethyl esters were administered to humans, EPA was found in the plasma free fatty acids and phospholipids within 4 h but did not appear in platelet phosphatidylcholine and phosphatidyletha-nolamine for 6 days. It was postulated that EPA may have entered megakaryocyte membranes rather than transferred directly to the platelets from plasma free fatty acids bound to albumin. further

Dietary fish oil in moderate or large doses has produced a modest prolongation of the bleeding time in normal persons. The lengthening of the bleeding time is most likely due to a mild inhibition of platelet aggregation, which has been observed when low concentrations of adenosine diphosphate (ADP) or collagen are used as aggregating agents. Feeding EPA and DHA ethyl esters also led to decreased platelet aggregation in response to low concentrations of collagen, although platelet aggregation to ADP was inhibited only when DHA was administered.

Fish oil feeding to normal subjects led to a decreased capacity of platelets to produce TXA2 after stimulation by aggregating agents ex vivo,120 which may be due to lowered concentrations of arachidonic acid in platelet membrane phospholipids, competition with arachidonic acid for cyclooxygenase by EPA, or by direct inhibition of cyclooxygenase by DHA. As previously mentioned, only small amounts of TXA3 with reduced biologic activity are synthesized because EPA is a relatively poor substrate for cyclooxygenase. The urinary excretion of endogenously produced thromboxane B2 metabolites (TXB2-M) in man are also reduced- and only small amounts of TXB3-M are found in normal subjects ingesting fish oil.