Dr. Preston Mason: High Concentration Mineral And Corn Oils Do Not Influence LDL Oxidation Rates

Two new studies sought to investigate whether placebo oils and their constituent fatty acids impact low-density lipoprotein (LDL) oxidation, which is a central mechanism of atherosclerosis. The studies were presented at the 2022 American Heart Association (AHA) Scientific Sessions

DocWire News spoke to R. Preston Mason, PhD, one of the principal investigators of the trial to learn more.

DocWire News: Can you give us some professional background on yourself?

Dr. Preston Mason: I’m glad to be with you today. My name is Preston Mason. I’m with Brigham and Women’s Hospital, affiliated with Harvard Medical School. I’ve been there for the last 21 years. And in the area of vascular biology and cardiovascular disease, I have investigated this area in my laboratory for the past 30 plus years.

Talk to us about the study you were an investigator on that was presented at the AHA’s Scientific Sessions 2022. How, and why was it conducted, and what were the results?

So we did a laboratory study investigating the effects of different placebo oils in a model of atherosclerosis. The two placebo oils we use have been used in recent trials involving omega-3 fatty acids. The two oils were mineral oil and corn oil. First of all, mineral oil is pharmaceutical grade. It’s made up of aliphatic chains, straight length aliphatic chains. And at pharmacologic levels, we looked at its ability to affect the oxidation of lipoproteins. We looked at lipoproteins because dietary fatty acids are transported on these particles, and when they are oxidized, they become highly atherogenic.

And so the question was, do these placebo oils influence this very important pathway of atherosclerosis and cardiovascular risk? And we found that they had no effect either way on oxidation. So they were completely benign, both the mineral oil and the corn oil. Then we looked at their constituents, even individual constituents of these oils. In the case of corn oil, for example, the primary constituent is linoleic acid, which is an omega-6 fatty acid. And in the case of mineral oil, we looked at different aliphatic chains and they themselves had no effect on oxidation, even at very high concentrations, concentrations that are much higher than would be expected in patients in clinical trials involving omega-3 fatty acids.

We furthermore compared it to omega-6 fatty acids. Excuse me, we compared it to omega-3 fatty acids. These are used in pharmaceutical preparations for the treatment of different things like high triglycerides and the case of EPA or eicosapentaenoic acid. A highly purified form is used to reduce the risk for heart disease in patients with mild hypertriglyceridemia. And we found that that particular formulation of EPA was highly affected in reducing lipoprotein oxidation, and that would be considered protective against heart diseases. That may be part of the explanation for the benefit that’s been seen in large outcome trials with that particular formulation using that omega-3 fatty acid, eicosapentaenoic acid or, or EPA, which is also icosapent ethyl in terms of the pharmaceutical formulation.

By contrast, another omega-3 fatty acid called DHA, or docosahexaenoic acid, failed to produce any substantial antioxidant benefit, which may be part of the explanation of why formulations involving DHA have failed to show any benefit in large well-done clinical outcome trials. So there appear to be differences among these omega-3 fatty acids with respect to their ability to protect against lipoprotein or LDL oxidation, and that may have important insights into the results of large outcome trials. And finally, the placebo oils again, had no effect even at very high concentrations that would not be expected to be seen in patients.

What were the limitations of this study?

The limitation of study, these are laboratory studies, so they’re done under very well controlled conditions. We would not give such high levels to patients, so that would not be appropriate. So the value of an in vitro study is we can look at it under very controlled conditions. We can look at even very high concentrations that would not be even seen in patients just to see where there might be any toxicity, if any. So those are the limitations. It was a laboratory in vitro study.

What are the clinical implications of the findings?

Well, there are many implications. First of all, there’s been some controversy whether placebo oil may be deleterious. And so the benefit seen with comparator agent or the active agent is not due to its inherent benefit, but due to the adverse effects of the mineral oil or other placebo oils. In this case, we did not see that at all. The mineral oil as expected and as seen in other clinical trials had very little effect, if any. In fact, mineral oils been used in dozens of trials, and there’s been no clear pattern that it causes adverse effects on lipids or inflammatory markers. So that was reassuring. Then the other important take home message is that EPA in particular and omega-3 fatty acid, as an omega-3 fatty acid, was very, very effective in reducing LDL oxidation, which could be part of the explanation for its pronounced clinical benefit in patients, even in patients who are already being well treated with other agents like statins.

Well, I think I will just tell you that many physicians talk to me at American Heart Association were very interested in this work, were relieved to know that these placebo oils indeed do not have any biologically active effects. And so we can have confidence in these outcome trials that show, or use these particular placebo oils, since they don’t seem to be biologically active or influence the risk for heart disease.