promega and Cardiovascular-Diseases

Dialysis patients have an inordinate risk of cardiovascular events. Fish oils, rich in n-3 fatty acids, are believed to be beneficial in the prevention of atherosclerosis and thrombosis. Hence, the use of fish oils deserves consideration as a preventative or therapeutic intervention in dialysis patients. The suggestion has been made that n-3 fatty acids could increase the risk of bleeding, and thus, the safety of the use of these agents in dialysis patients must be established before long-term studies are undertaken. This study addresses the effect of n-3 fatty acids on the hemostatic profile of dialysis patients. Sixteen patients on chronic dialysis therapy were randomized to fish oil (MaxEPA) or placebo (olive oil) in a double-blind cross-over study. They received 3.6 g of n-3 fatty acids for 4 wk. Bleeding times were 4.8 +/- 0.4 min on MaxEPA and 4.5 +/- 0.3 min on placebo. Platelet aggregation to low-dose ADP or collagen also remained unchanged. There was a trend to lower serum triglyceride levels (2.7 +/- 0.5 versus 3.4 +/- 0.6 mmol/L, fish oil versus placebo) that did not reach statistical significance. Gastrointestinal side effects occurred in 10 of the 16 subjects and were severe in 5 patients. These side effects occurred in both the olive oil and the fish oil groups. The study had a 95% chance of detecting a clinically doubling significant increase in bleeding time, i.e., beta error less than 5%. In conclusion, n-3 fatty acids do not introduce a clinically important risk of bleeding for patients with end-stage renal disease.

Topics: Adult; Aged; Blood Pressure; Cardiovascular Diseases; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Fish Oils; Hemostasis; Humans; Kidney Failure, Chronic; Lipids; Male; Middle Aged; Peritoneal Dialysis; Renal Dialysis

The aim of this study was to evaluate the effects of a fish oil preparation (MaxEPA) on hemostatic function and fasting lipid and glucose levels in non-insulin-dependent diabetic (NIDDM) subjects. Eighty NIDDM outpatients aged 55.9 yr (mean SD 11.5 yr) participated in a prospective double-blind placebo-controlled study of MaxEPA capsules (10 g/day) or olive oil (control) treatment over 6 wk. Patients received either MaxEPA or olive oil in addition to preexisting therapy. Metabolic and hemostatic variables were measured before treatment and after 3 and 6 wk. Platelet membrane eicosapentaenoic acid (EPA) content increased in the treatment group (P less than 0.001). MaxEPA supplementation was associated with a significant fall in total triglycerides (P less than 0.001) but did not affect total cholesterol (P = 0.7) compared with control treatment. Fasting plasma glucose increased after 3 wk (P = 0.01) but not after 6 wk (P = 0.17) treatment with MaxEPA. Spontaneous platelet aggregation in whole blood fell in the MaxEPA group (P less than 0.02) after 6 wk, but there were no changes in agonist-induced platelet aggregation, thromboxane generation in platelet-rich plasma, or plasma beta-thromboglobulin and platelet factor IV levels. An increase in clotting factor VII (P = 0.02), without changes in fibrinogen or factor X levels, occurred in the MaxEPA group. Similar reductions in blood pressure were observed in both groups. Dietary supplementation with MaxEPA capsules (10 g/day) in NIDDM subjects is associated with improvement in hypertriglyceridemia but with deleterious effects in factor VII and blood glucose levels. Most indices of platelet function are unaffected by this therapy.

Topics: Blood Glucose; Cardiovascular Diseases; Cholesterol; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diet, Diabetic; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Fish Oils; Food, Fortified; Hemostasis; Humans; Lipids; Male; Thromboxane B2; Triglycerides

Serum triacylglycerols (TG), VLDL, HDL, fatty acid and eicosanoid spectrum are among the factors determining the risk of cardiovascular complications in NIDDM. N-3 polyunsaturated fatty acids (PUFA) are expected to have beneficial effects on these factors. In NIDDM patients there have however been previously reported (late 1980s) some adverse effects.. Our aim was to verify the effects of n-3 PUFA in NIDDM patients using relatively low dosage.. The investigated group included 21 NIDDM patients with dyslipoproteinemia type IV. The patients were treated for 28 days with 1.7 g EPA (eicosapentaenoic acid) + 1.15 g DHA (docosahexaenoic acid)/day (10 capsules/day of MAXEPA, Seven Seas U.K.). The lipoproteins were measured using the BIO-LACHEMA kits, the fatty acid spectrum in phospholipids was determined by gas chromatography and prostanoids (after their separation) were measured by RIA methods.. After the MAXEPA treatment there has been a strong decrease in TG (p < 0.005) and VLDL (p < 0.002) serum levels, accompanied by a significant increase in HDL (p < 0.02). The final-to-baseline TG ratio in individual patients negatively correlated with the relative percentage of EPA in phospholipids after the treatment (p < 0.03; r = -0.474). There was no significant change in serum total cholesterol, fasting glycaemia and glycosylated hemoglobin. There was a slight, but statistically already significant (p < 0.05), rise in LDL. The relative percentage of EPA, docosapentaenoic acid and DHA in serum phospholipids increased sharply (p < 0.001, p < 0.001, p < 0.001). The increase of n-3 PUFA in individual patients was linked with the decrease in n-6 PUFA (p < 0.001; r = -0.686). The spectrum of the latter has changed also very markedly. The prostacyclin PGI2-to-thromboxane TxA2 ratio increased significantly (p < 0.001). Beneficial effects of n-3 fatty acids have prevailed and this kind of treatment seems very encouraging also in NIDDM patients. The results are logically compatible with other authors' results pattern formed in 1990s. A slight rise in serum LDL needs a more detailed discussion since only its phenotype B ("small dense LDL particles") has been recently found to be atherogenic. (Tab. 2, Fig. 5, Ref. 15.)

Topics: Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, VLDL; Diabetes Mellitus, Type 2; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Fish Oils; Humans; Hyperlipoproteinemia Type IV; Male; Middle Aged; Risk Factors; Triglycerides

Haemodialysis patients have an exceptionally high incidence of death from cardiovascular causes, related in part to abnormalities of lipids and platelets. Eskimos, however, have a low incidence of myocardial infarction and have a high dietary intake of fish, rich in omega-3 polyunsaturated fatty acids. We have, therefore, studied the effect of a fish oil MaxEPA, containing 3.6 g of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid on lipids and platelet function in haemodialysis patients. Following 8 weeks of therapy there was a 35% fall in triglycerides, a 10% rise of high-density lipoprotein (HDL) cholesterol, a 36% rise of HDL2 cholesterol fraction and a 54% rise of the HDL2:HDL3 cholesterol ratio. The platelet aggregation to adenosine diphosphate and collagen was significantly reduced. The activated whole-blood clotting time was prolonged from 141 to 153 s, and 69% of patients showed a reduction of factor VIII related antigen which is usually elevated in haemodialysis patients and is thought to be a marker of endothelial damage. The blood pressure fell from 147/82 to 124/74. We have thus shown that a dietary supplement of eicosapentaenoic acid produces potentially beneficial effects on lipids, platelets, and blood pressure and may help to protect against atheroma and thus cardiovascular mortality in high-risk haemodialysis patients.

Topics: Adolescent; Adult; Arteriosclerosis; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Female; Humans; Lipids; Male; Middle Aged; Platelet Aggregation; Renal Dialysis; Triglycerides