Effect of fish oil on LDL oxidation and plasma homocysteine concentrations in health.
Oxidation of low-density lipoprotein (LDL) and hyperhomocysteinemia are believed to play a role in therogenesis. Whether n-3 polyunsaturated fatty acids increase LDL susceptibility to oxidation or influence homocysteine (Hcy) metabolism has long been a subject of controversy. In this study, we evaluated the effect of 8 weeks of dietary supplementation with 6 g/day of fish oil (FO; 3 g of n-3 fatty acids) on plasma lipoproteins, in vitro LDL peroxidation, antioxidant status, and plasma Hcy concentrations in 16 normolipidemic subjects. FO rapidly and significantly (P < .01) decreased plasma total and very low density lipoprotein triglyceride concentrations and had no effect on LDL or high-density-lipoprotein cholesterol. The mean lag time before onset of Cu(2+)-induced LDL oxidation, as well as plasma and LDL alpha-tocopherol and beta-carotene concentrations, was unchanged. However, changes in plasma aminothiol concentrations occurred during the study. Specifically, a progressive and significant increase in total Hcy plasma concentrations was observed (13.4% and 20% after 4 and 8 weeks, respectively; P < .01). Total glutathione concentrations were significantly higher after 8 weeks (P < .05). The tHcy increase was not associated with changes in plasma folate or vitamin B(12) concentrations. However, concentrations of plasma nitric oxide metabolites (NO(x) = NO(2) + NO(3)) were significantly higher than at baseline after 8 weeks of FO intake (74%; P < .01). Further, the changes in total Hcy and NO(x) plasma concentrations observed after 8 weeks of FO were found to be significantly correlated (r = .78, P < .001). With this study, we report for the first time the apparent interaction of n-3 fatty acids and nitric oxide on Hcy metabolism.
Piolot
Alain
A
Hyperlipidemia and Atherosclerosis Research Group of the Clinical Research Institute of Montreal and INSERM-U498-Faculté de Médecine, Université de Bourgogne, Dijon, Canada.
Blache
Denis
D
Boulet
Lucie
L
Fortin
Louis Jacques
LJ
Dubreuil
Denise
D
Marcoux
Caroline
C
Davignon
Jean
J
Lussier-Cacan
Suzanne
S
D000328:Adult; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003300:Copper / Q000494:pharmacology; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000097:blood; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage*; D005978:Glutathione / Q000097:blood; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014280:Triglycerides / Q000097:blood; D024502:alpha-Tocopherol / Q000097:blood; D019207:beta Carotene / Q000097:blood
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D008077:Lipoproteins, LDL; D009566:Nitrates; D009573:Nitrites; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides; D019207:beta Carotene; D006710:Homocysteine; D009569:Nitric Oxide; D003300:Copper; D005978:Glutathione; D024502:alpha-Tocopherol