• Harris, William (PI)

Project: Research project

Project Details


The low incidence of cardiovascular diseases among fish-eating
populations has led to the hypothesis that fish oils containing
omega-3 fatty acids (w3 FA) may be protective agents. Clinical
studies have shown that high intakes of fish oils cause total
cholesterol and, particularly, triglyceride levels to fall in normals
and hyperlipidemic patients. Although in these studies low
density lipoprotein (LDL) cholesterol levels were reduced, recent
studies utilizing more practical intakes of fish oil (less than 20
gm/day) have found significant elevations in LDL cholesterol
levels, especially in patients with hypertriglyceridemia (HTG).
Thus, the usefulness of fish oil may be limited in this population.
We propose to study very low density lipoprotein (VLDL) and LDL
apolipoprotein B metabolism in 32 HTG patients given fish oil vs.
a vegetable oil control. They will receive 12, 1-gm capsules of
the oils per day for 2, randomly assigned, 6-week periods. In 8
HTG patients with familial combined hyperlipidemia (FCHL) and 8
with familial hypertriglyceridemia (FHTG), the kinetics of 2
VLDL subfractions will be studied during each of the two
treatment phases. In a different group of 8 FCHL and 8 FHTG
patients, LDL kinetic studies will be done. Also, changes in the
chemical composition of VLDL and LDL will be measured by
combined ultracentrifugation and column chromatography in both
groups of HTG patients and in a group of 8 normal subjects. We
should be able to determine whether the increase in LDL
cholesterol in HTG patients given fish oil supplements is the
result of 1) increased conversion of large and/or small VLDL to
LDL, 2) direct hepatic secretion of LDL, 3) decreased removal of
LDL from the plasma because of increased competition from
small VLDL for removal mechanisms, or 4) decreased removal of
LDL because of a direct effect of w3 FA on receptor or non-
receptor mediated pathways. These studies should reveal the
mechanisms by which w3 FA supplements alter lipoprotein
metabolism in HTG patients.
Effective start/end date7/1/8812/31/94


  • National Institutes of Health: $84,654.00
  • National Institutes of Health: $91,615.00


  • Medicine(all)


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