The epidemiological evidence that populations consuming diets rich in Omega(Omega)-3 fatty acids derived from marine animals have lower plasma lipid levels and increased bleeding times has now been confirmed in metabolic balance studies. Normal and hyperlipidemic humans were fed three different diets: """"""""saturated"""""""" fat; high """"""""Omega-3"""""""" fatty acids from salmon and fish oil; and a high """"""""Omega-6' diet from safflower oil. The """"""""high Omega-3"""""""" diet lowered plasma cholesterol, LDL, triglyceride and VLDL versus the control diet. The VLDL lowering effect was especially pronounced in hypertriglyceridemic patients (types II-b, IV and V); no triglyceride lowering occurred from the """"""""Omega-6"""""""" diet. The """"""""high Omega-3"""""""" diet was antithrombotic in that bleeding times increased and platelet aggregation was reduced in contrast to both control diets (the saturated fat and Omega-6 diets). The proposed new studies were designed to explore the mechanisms of the hypotriglyceridemic and platelet effects of Omega-3 fatty acids in human beings under controlled dietary conditions. The synthesis and removal of plasma triglyceride, VLDL and LDL would be determined in labelled turnover studies. The effects of Omega-3 fatty acids upon the synthesis of triglyceride and VLDL would be explored in primary liver cell cultures from experimental animals. The absorption of dietary Omega-3 fatty acids into the body and subsequent chylomicron formation and clearance would be measured in both humans and rats. The minimum amount of dietary Omega-3 fatty acids which would affect the plasma lipids and platelet function would be determined. The long term efficacy and toxicity Omega-3 fatty acids would be evaluated in hyperlipidemic patients. Their effects upon platelet count, size and composition would be measured. In addition, thromboxane and prostacyclin survival would be studied in plasma during fish oil and control periods. In particular, the reason for the thrombocytopenic effect of dietary Omega-3 fatty acids will be explored by radio-labelled platelet turnover studies. Since this unique class of dietary fatty acids may potentially be important in preventing and treating atherosclerotic and thrombotic diseases, it is now necessary to establish mechanisms of action, long term efficacy and possible untoward effects.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL025687-08
Application #
3338205
Study Section
Metabolism Study Section (MET)
Project Start
1980-04-01
Project End
1988-09-30
Budget Start
1987-04-01
Budget End
1988-09-30
Support Year
8
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
Lin, D S; Connor, W E; Spenler, C W (1993) Are dietary saturated, monounsaturated, and polyunsaturated fatty acids deposited to the same extent in adipose tissue of rabbits? Am J Clin Nutr 58:174-9
Weidner, G; Connor, S L; Hollis, J F et al. (1992) Improvements in hostility and depression in relation to dietary change and cholesterol lowering. The Family Heart Study. Ann Intern Med 117:820-3
Rapp, J H; Connor, W E; Lin, D S et al. (1991) Dietary eicosapentaenoic acid and docosahexaenoic acid from fish oil. Their incorporation into advanced human atherosclerotic plaques. Arterioscler Thromb 11:903-11
Lin, D S; Connor, W E; Anderson, G J (1991) The incorporation of n-3 and n-6 essential fatty acids into the chick embryo from egg yolks having vastly different fatty acid compositions. Pediatr Res 29:601-5
Weidner, G; Connor, S L; Chesney, M A et al. (1991) Sex differences in high density lipoprotein cholesterol among low-level alcohol consumers. Circulation 83:176-80
Harris, W S; Rothrock, D W; Fanning, A et al. (1990) Fish oils in hypertriglyceridemia: a dose-response study. Am J Clin Nutr 51:399-406
Harris, W S; Connor, W E; Illingworth, D R et al. (1990) Effects of fish oil on VLDL triglyceride kinetics in humans. J Lipid Res 31:1549-58
Benner, K G; Sasaki, A; Gowen, D R et al. (1990) The differential effect of eicosapentaenoic acid and oleic acid on lipid synthesis and VLDL secretion in rabbit hepatocytes. Lipids 25:534-40
Ruyle, M; Connor, W E; Anderson, G J et al. (1990) Placental transfer of essential fatty acids in humans: venous-arterial difference for docosahexaenoic acid in fetal umbilical erythrocytes. Proc Natl Acad Sci U S A 87:7902-6
Goodnight Jr, S H (1989) The vascular effects of omega-3 fatty acids. J Invest Dermatol 93:102S-106S

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