Effects of low-dose EPA-E on glycemic control, lipid profile, lipoprotein(a), platelet aggregation, viscosity, and platelet and vessel wall interaction in NIDDM.
OBJECTIVE
To assess the effects of low-dose eicosapentaenoic acid-ethyl-ester on diabetes regulation, lipid metabolism, blood rheology, and platelet reactivity.


METHODS
In a double-blind, randomized, placebo-controlled study, 24 NIDDM subjects received 1800 mg of EPA-E, 900 mg of EPA-E, or a placebo (1656 mg olive oil) daily for 8 wk.


RESULTS
The EPA:arachidonic acid plasma ratio increased over an 8-wk period, then declined after a 4-wk wash-out period in the fish-oil groups in a dose-dependent way. Platelet-activating factor-induced platelet aggregation decreased from 75 +/- 7% at wk 0 to 35 +/- 21% at wk 8 in the 900-mg group (P = 0.016) and from 72 +/- 11 to 40 +/- 30% in the 1800-mg group (P = 0.039), but did not change in the placebo group. No effects on ADP- or collagen-induced aggregation could be attributed to EPA-E. In the 1800-mg group low-density-lipoprotein cholesterol increased significantly, without concomitant rise in apolipoprotein B. Triglycerides, glycemic control, lipoprotein (a), blood and plasma viscosity, erythrocyte deformability, and platelet adhesion to and aggregate formation on extracellular endothelial cell matrix were not significantly influenced.


CONCLUSIONS
Purified EPA-E in doses of 900 and 1800 mg reduces Platelet-activating factor-induced platelet aggregation without negatively affecting glycemic control. Low-density-lipoprotein cholesterol was elevated in the 1800-mg group.
Department of Internal Medicine and Hematology, University Hospital Utrecht, The Netherlands.
H T
HT
Westerveld
J C
JC
de Graaf
H H
HH
van Breugel
J W
JW
Akkerman
J J
JJ
Sixma
D W
DW
Erkelens
J D
JD
Banga
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D001809:Blood Viscosity / Q000187:drug effects*; D003094:Collagen / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000502:physiology; D004907:Erythrocyte Deformability / Q000187:drug effects; D005109:Extracellular Matrix / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010972:Platelet Activating Factor / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects*
D001786:Blood Glucose; D017270:Lipoprotein(a); D010972:Platelet Activating Factor; D000244:Adenosine Diphosphate; C035276:eicosapentaenoic acid ethyl ester; D003094:Collagen; D015118:Eicosapentaenoic Acid