Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1984 Jul;74(1):82–89. doi: 10.1172/JCI111422

Suppression by diets rich in fish oil of very low density lipoprotein production in man.

P J Nestel, W E Connor, M F Reardon, S Connor, S Wong, R Boston
PMCID: PMC425187  PMID: 6736254

Abstract

The highly polyunsaturated fatty acids in fish oils lower the plasma triglyceride concentration. We have studied the effect of a diet rich in fish oil on the rate of production of the triglyceride-transporting very low density lipoprotein (VLDL). Seven subjects, five normal and two with hypertriglyceridemia received up to 30% of daily energy needs from a fish oil preparation that was rich in eicosapentaenoic acid and docosahexaenoic acid, omega-3 fatty acids with five and six double bonds, respectively. Compared with a diet similarly enriched with safflower oil (in which the predominant fatty acid is the omega-6 linoleic acid, with two double bonds), the fish oil diet lowered VLDL lipids and B apoprotein concentrations profoundly. High density lipoprotein lipids and A1 apoprotein were also lowered, but the effect on low density lipoprotein (LDL) concentration was inconsistent. The daily production or flux of VLDL apoprotein B, calculated from reinjected autologous 125I-labeled lipoprotein, was substantially less in six subjects studied after 3 wk of fish oil, compared with after safflower oil. This effect on flux was more consistent than that on the irreversible fractional removal rate, which was increased in the four normolipidemic but inconsistent in the hypertriglyceridemic subjects. This suggests that fish oil reduced primarily the production of VLDL. The daily production of VLDL triglyceride, calculated from the kinetics of the triglyceride specific radioactivity-time curves after [3H]glycerol was injected, also showed very substantial reductions in five subjects studied. The marked suppression in VLDL apoprotein B and VLDL triglyceride formation was found not to be due to diminished plasma total free fatty acid or plasma eicosapentaenoic flux, calculated during constant infusions of [14C]eicosapentaenoic acid and [3H]oleic acid in four subjects. In two subjects there was presumptive evidence for substantial independent influx of LDL during the fish oil diet, based on the precursor-product relationship between the intermediate density lipoprotein and LDL apoprotein B specific radioactivity-time curves.

Full text

PDF

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AHRENS E. H., Jr, INSULL W., Jr, BLOMSTRAND R., HIRSCH J., TSALTAS T. T., PETERSON M. L. The influence of dietary fats on serum-lipid levels in man. Lancet. 1957 May 11;272(6976):943–953. doi: 10.1016/s0140-6736(57)91280-1. [DOI] [PubMed] [Google Scholar]
  2. Bronsgeest-Schoute H. C., van Gent C. M., Luten J. B., Ruiter A. The effect of various intakes of omega 3 fatty acids on the blood lipid composition in healthy human subjects. Am J Clin Nutr. 1981 Sep;34(9):1752–1757. doi: 10.1093/ajcn/34.9.1752. [DOI] [PubMed] [Google Scholar]
  3. Chait A., Onitiri A., Nicoll A., Rabaya E., Davies J., Lewis B. Reduction of serum triglyceride levels by polyunsaturated fat. Studies on the mode of action and on very low density lipoprotein composition. Atherosclerosis. 1974 Sep-Oct;20(2):347–364. doi: 10.1016/0021-9150(74)90017-3. [DOI] [PubMed] [Google Scholar]
  4. Cortese C., Levy Y., Janus E. D., Turner P. R., Rao S. N., Miller N. E., Lewis B. Modes of action of lipid-lowering diets in man: studies of apolipoprotein B kinetics in relation to fat consumption and dietary fatty acid composition. Eur J Clin Invest. 1983 Feb;13(1):79–85. doi: 10.1111/j.1365-2362.1983.tb00068.x. [DOI] [PubMed] [Google Scholar]
  5. Curry M. D., Alaupovic P., Suenram C. A. Determination of apolipoprotein A and its constitutive A-I and A-II polypeptides by separate electroimmunoassays. Clin Chem. 1976 Mar;22(3):315–322. [PubMed] [Google Scholar]
  6. Davis R. A., Boogaerts J. R. Intrahepatic assembly of very low density lipoproteins. Effect of fatty acids on triacylglycerol and apolipoprotein synthesis. J Biol Chem. 1982 Sep 25;257(18):10908–10913. [PubMed] [Google Scholar]
  7. Fidge N. H., Poulis P. Metabolic heterogeneity in the formation of low density lipoprotein from very low density lipoprotein in the rat: evidence for the independent production of a low density lipoprotein subfraction. J Lipid Res. 1978 Mar;19(3):342–349. [PubMed] [Google Scholar]
  8. Goodman D. S., Noble R. P. Turnover of plasma cholesterol in man. J Clin Invest. 1968 Feb;47(2):231–241. doi: 10.1172/JCI105719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Harris W. S., Connor W. E., McMurry M. P. The comparative reductions of the plasma lipids and lipoproteins by dietary polyunsaturated fats: salmon oil versus vegetable oils. Metabolism. 1983 Feb;32(2):179–184. doi: 10.1016/0026-0495(83)90226-3. [DOI] [PubMed] [Google Scholar]
  11. Harris W. S., Connor W. E. The effects of salmon oil upon plasma lipids, lipoproteins, and triglyceride clearance. Trans Assoc Am Physicians. 1980;93:148–155. [PubMed] [Google Scholar]
  12. Holmquist L., Carlson K., Carlson L. A. Comparison between the use of isopropanol and tetramethylurea for the solubilisation and quantitation of human serum very low density apolipoproteins. Anal Biochem. 1978 Aug 1;88(2):457–460. doi: 10.1016/0003-2697(78)90444-x. [DOI] [PubMed] [Google Scholar]
  13. Janus E. D., Nicoll A., Wootton R., Turner P. R., Magill P. J., Lewis B. Quantitative studies of very low density lipoprotein: conversion to low density lipoprotein in normal controls and primary hyperlipidaemic states and the role of direct secretion of low density lipoprotein in heterozygous familial hypercholesterolaemia. Eur J Clin Invest. 1980 Apr;10(2 Pt 1):149–159. doi: 10.1111/j.1365-2362.1980.tb02075.x. [DOI] [PubMed] [Google Scholar]
  14. Kohout M., Kohoutova B., Heimberg M. The regulation of hepatic triglyceride metabolism by free fatty acids. J Biol Chem. 1971 Aug 25;246(16):5067–5074. [PubMed] [Google Scholar]
  15. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  16. Lin D. S., Connor W. E. The long term effects of dietary cholesterol upon the plasma lipids, lipoproteins, cholesterol absorption, and the sterol balance in man: the demonstration of feedback inhibition of cholesterol biosynthesis and increased bile acid excretion. J Lipid Res. 1980 Nov;21(8):1042–1052. [PubMed] [Google Scholar]
  17. NOVAK M. COLORIMETRIC ULTRAMICRO METHOD FOR THE DETERMINATION OF FREE FATTY ACIDS. J Lipid Res. 1965 Jul;6:431–433. [PubMed] [Google Scholar]
  18. Neri B. P., Frings C. S. Improved method for determination of triglycerides in serum. Clin Chem. 1973 Oct;19(10):1201–1202. [PubMed] [Google Scholar]
  19. Nestel P. J., Barter P. J. Triglyceride clearance during diets rich in carbohydrate or fats. Am J Clin Nutr. 1973 Mar;26(3):241–245. doi: 10.1093/ajcn/26.3.241. [DOI] [PubMed] [Google Scholar]
  20. Nestel P. J., Barter P. Metabolism of palmitic and linoleic acids in man: differences in turnover and conversion to glycerides. Clin Sci. 1971 Apr;40(4):345–350. doi: 10.1042/cs0400345. [DOI] [PubMed] [Google Scholar]
  21. Nestel P. J. Relationship between FFA flux and TGFA influx in plasma before and during the infusion of insulin. Metabolism. 1967 Dec;16(12):1123–1132. doi: 10.1016/0026-0495(67)90058-3. [DOI] [PubMed] [Google Scholar]
  22. Nestel P., Tada N., Billington T., Huff M., Fidge N. Changes in very low density lipoproteins with cholesterol loading in man. Metabolism. 1982 Apr;31(4):398–405. doi: 10.1016/0026-0495(82)90117-2. [DOI] [PubMed] [Google Scholar]
  23. STEINBERG D., NESTEL P. J., BUSKIRK E. R., THOMPSON R. H. CALORIGENIC EFFECT OF NOREPINEPHRINE CORRELATED WITH PLASMA FREE FATTY ACID TURNOVER AND OXIDATION. J Clin Invest. 1964 Feb;43:167–176. doi: 10.1172/JCI104901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sanders T. A., Vickers M., Haines A. P. Effect on blood lipids and haemostasis of a supplement of cod-liver oil, rich in eicosapentaenoic and docosahexaenoic acids, in healthy young men. Clin Sci (Lond) 1981 Sep;61(3):317–324. doi: 10.1042/cs0610317. [DOI] [PubMed] [Google Scholar]
  25. Schonfeld G., Patsch W., Rudel L. L., Nelson C., Epstein M., Olson R. E. Effects of dietary cholesterol and fatty acids on plasma lipoproteins. J Clin Invest. 1982 May;69(5):1072–1080. doi: 10.1172/JCI110542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Shepherd J., Packard C. J., Patsch J. R., Gotto A. M., Jr, Taunton O. D. Effects of dietary polyunsaturated and saturated fat on the properties of high density lipoproteins and the metabolism of apolipoprotein A-I. J Clin Invest. 1978 Jun;61(6):1582–1592. doi: 10.1172/JCI109078. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Stansby M. E. Nutritional properties of fish oils. World Rev Nutr Diet. 1969;11:46–105. doi: 10.1159/000387575. [DOI] [PubMed] [Google Scholar]
  28. Vega G. L., Groszek E., Wolf R., Grundy S. M. Influence of polyunsaturated fats on composition of plasma lipoproteins and apolipoproteins. J Lipid Res. 1982 Aug;23(6):811–822. [PubMed] [Google Scholar]
  29. Warnick G. R., Albers J. J. A comprehensive evaluation of the heparin-manganese precipitation procedure for estimating high density lipoprotein cholesterol. J Lipid Res. 1978 Jan;19(1):65–76. [PubMed] [Google Scholar]
  30. Wong S. H., Nestel P. J., Trimble R. P., Storer G. B., Illman R. J., Topping D. L. The adaptive effects of dietary fish and safflower oil on lipid and lipoprotein metabolism in perfused rat liver. Biochim Biophys Acta. 1984 Feb 9;792(2):103–109. doi: 10.1016/0005-2760(84)90209-1. [DOI] [PubMed] [Google Scholar]
  31. Zech L. A., Grundy S. M., Steinberg D., Berman M. Kinetic model for production and metabolism of very low density lipoprotein triglycerides. Evidence for a slow production pathway and results for normolipidemic subjects. J Clin Invest. 1979 Jun;63(6):1262–1273. doi: 10.1172/JCI109421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. von Lossonczy T. O., Ruiter A., Bronsgeest-Schoute H. C., van Gent C. M., Hermus R. J. The effect of a fish diet on serum lipids in healthy human subjects. Am J Clin Nutr. 1978 Aug;31(8):1340–1346. doi: 10.1093/ajcn/31.8.1340. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES