Summary
This study looked at how different types of dietary fat—specifically oleic acid (a monounsaturated fat) versus linoleic acid (a polyunsaturated omega-6 fat)—change the composition of LDL and HDL cholesterol in the body, and how those changes affect their vulnerability to oxidation, a key step in the development of atherosclerosis.
Mildly hypercholesterolemic adults were fed either oleate-rich or linoleate-rich diets for eight weeks. Afterward, researchers examined how the participants’ LDL and HDL particles behaved under oxidative stress in the lab.
The differences were striking:
LDL from people eating oleate-rich diets was far more resistant to oxidation. It produced fewer lipid peroxides and fewer conjugated dienes—two major markers of oxidative damage.
This oleate-rich LDL was also less likely to be taken up and degraded by macrophages after oxidation, a process tied to plaque buildup in arteries.
In contrast, LDL from those consuming more linoleic acid was much more prone to oxidation.
Across all participants, the more linoleic acid (18:2) found in LDL particles, the more easily the LDL oxidized—a relationship so strong that correlations were 0.89 and 0.71 for major oxidative markers (p < 0.01).
HDL composition also changed with diet, but reassuringly, HDL from both groups maintained its ability to protect LDL from oxidative damage.
Overall, the study shows that what we eat changes the actual fatty-acid makeup of our LDL and HDL, and this directly influences how easily LDL oxidizes. Because oxidized LDL is central to atherosclerosis, the findings suggest an important takeaway:
Replacing saturated fats with monounsaturated fats (like oleic acid from olive oil) may be safer and more protective than replacing them with polyunsaturated omega-6 fats (like linoleic acid).
This supports the idea that monounsaturated fats may help reduce cardiovascular risk by making LDL more resilient and less likely to contribute to plaque formation.
PMID: 8432867
PMCID: PMC288008
DOI: 10.1172/JCI116247
Abstract
We report the results of feeding oleate- or linoleate-enriched diets for 8 wk to mildly hypercholesterolemic subjects and the resulting alterations in composition and functional properties of their plasma LDL and HDL. LDL isolated from subjects on oleate-enriched diets was less susceptible to copper-mediated oxidation, as measured by conjugated diene and lipid peroxide formation, and less susceptible to LDL-protein modification, as evidenced by reduced LDL macrophage degradation after copper- or endothelial cell-induced oxidation. For all subjects, the percentage of 18:2 in LDL correlated strongly with the extent of conjugated diene formation (r = 0.89, P < 0.01) and macrophage degradation (r = 0.71, P < 0.01). Oxidation of LDL led to initial rapid depletion of unsaturated fatty acids in phospholipids followed by extensive loss of unsaturated fatty acids in cholesteryl esters and triglycerides. Changes in HDL fatty acid composition also occurred. However, HDL from both dietary groups retained its ability to inhibit oxidative modification of LDL. This study demonstrates that alterations in dietary fatty acid composition can effectively alter the fatty acid distribution of LDL and HDL in hypercholesterolemic subjects and that susceptibility to LDL oxidation is altered by these changes. Substitution of monounsaturated (rather than polyunsaturated) fatty acids for saturated fatty acids in the diet might be preferable for the prevention of atherosclerosis.
Reaven P, Parthasarathy S, Grasse BJ, Miller E, Steinberg D, Witztum JL. Effects of oleate-rich and linoleate-rich diets on the susceptibility of low density lipoprotein to oxidative modification in mildly hypercholesterolemic subjects. J Clin Invest. 1993 Feb;91(2):668-76. doi: 10.1172/JCI116247. PMID: 8432867; PMCID: PMC288008.