High dose eicosapentaenoic acid ethyl ester: effects on lipids and neutrophil leukotriene production in normal volunteers.
1. A 93% pure ethyl ester of eicosapentaenoic acid was investigated for tolerability and biochemical effects on neutrophil leukotriene synthesis and plasma lipoproteins when given in high dose. Six healthy volunteers received 6 g eicosapentaenoic acid ethyl ester daily for 6 weeks, followed by a 4 week wash-out and then 18 g daily for 6 weeks. 2. There was inhibition of neutrophil leukotriene B4 and 5-hydroxyeicosatetraenoic acid synthesis, with no significant differences between low and high dose. 3. There was a dose dependent increase in leukotriene B5 and 5-hydroxyeicosatetraenoic acid acid synthesis. 4. Plasma triglycerides were reduced maximally on 6 g daily, with no greater suppression at 18 g daily. 5. Plasma cholesterol was only suppressed significantly at 18 g daily. 6. The 6 g daily dose was well tolerated but the 18 g daily dose produced diarrhoea and steatorrhoea.
Hawthorne
A B
AB
Department of Therapeutics, University Hospital, Nottingham.
Filipowicz
B L
BL
Edwards
T J
TJ
Hawkey
C J
CJ
D000328:Adult; D002784:Cholesterol / Q000097:blood; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000187:drug effects; D005227:Fatty Acids / Q000097:blood; D006801:Humans; D007975:Leukotriene B4 / Q000097:blood*; D008055:Lipids / Q000097:blood*; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D005227:Fatty Acids; D008055:Lipids; D014280:Triglycerides; D007975:Leukotriene B4; C035276:eicosapentaenoic acid ethyl ester; D002784:Cholesterol; D015118:Eicosapentaenoic Acid