Fish oils have been at or near the center of the public’s obsession with health supplements for many decades. The epidemiologic data linking improved health, particularly cardiovascular well being, have been part of accepted health folklore to the point that health care providers just accept our patients taking such supplements as part of their attempts to optimize self-care. The nutriceutical industry has complied by coming up with different names, compounds, formulations, variations, slick advertising on television and print and online media, all targeted to grab a part of one’s discretionary income. These agents often have been rather expensive, but certainly less expensive than many branded pharmaceuticals, and certainly less expensive than developing the diseases these agents are touted to prevent.
The underlying thought amongst most evidence-based practitioners has been that fish oils, in their natural form, that is, in fish, have indeed been truly healthful and beneficial for the nutrition and cardiovascular health of our patients. But many people don’t like fish for a variety of reasons, or have difficulty in procuring fish, but want to have the ostensible health benefits of eating fish. Hence, the opportunity to perhaps distill, literally, the essential beneficial essence of fish into a reasonably palatable form and provide that to potential consumers. So far, so good.
Now it starts to get a bit murky and confusing. Fish oils are derived from fish consuming a food chain that begins with plankton up to other sea creatures that eat healthily, barring human contamination of their food chain with PCBs, dioxin, mercury, etc.. These fish oils are complex mixtures of numerous, mostly polyunsaturated and liquid, fats which are not solid at their normal body temperatures. The liquidity is mostly a function of their being polyunsaturated, which means in chemistry that multiple carbon atoms in these relatively long carbon chains are double bonded to each other. Saturated means that these double bonds are converted to single bonds, often induced by exposure to oxygen, which also means that these now “saturated” fats are solid at room temperature. This is why polyunsaturated olive oil is a liquid at room temperature, and saturated fats, like butter, are solid. And good plant oils that naturally have unsaturated bonds, are saturated (with hydrogen) to give them a long shelf life, hence you now have “margarine,” which is why you see the term “hydrogenated” in their label. You see, unsaturated fats in fish oils, which are good for you, get saturated and bad for you when they are exposed to air, or more specifically, oxygen. This is why fish “go bad and smell”: their polyunsaturated fats have become saturated when oxidized when exposed to air, even when refrigerated, as most of us know all too well.
Of the many forms of oils in fish oils, the dominant types that seem to be beneficial for human health are EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). These are important for growth and health of the nervous system, and can be derived from plant as well as marine sources. The vast majority of fish oil supplements have mixed formulations of both EPA and DHA, usually listed on the product label. But as we focus on cardiovascular health, EPA and DHA may have important differences in their effects on your blood fats. EPA lowers LDL-cholesterol (bad cholesterol), and DHA seems to raise LDL-C. These data may explain some of the confusion that have surrounded the fish oil reports that have been reported in the media.
There have been numerous meta-analyses (the forced combining of multiple disparate research protocols to see if some sense or hypotheses can be derived by pooling the results) of fish oils that have not shown reduction in serious cardiovascular events like heart attacks, strokes, or mortality, despite the advertising you see from their manufacturers. These fish oils have always been capsules containing combinations of both EPA and DHA. At the American Heart Association meeting last November in Chicago, and in the prestigious New England Journal of Medicine, two well conducted randomized, double blinded, placebo controlled fish oil trials, called ASCEND and VITAL, were also reported and also showed no cardiovascular benefit of fish oils. Seemingly, this would seem to have settled the issue about the value of fish oils.
But the REDUCE-IT trial, published in the first January edition of the New England Journal of Medicine may change the fish oil paradigm and has the potential to alter the way doctors will manage cardiovascular risk in the future. For the first time, a specific fish oil preparation has reduced the incidence of heart attacks, stroke, revascularization and cardiovascular mortality comparable to and perhaps exceeding that achieved with statins and other cholesterol lowering agents. Moreover, these results do not seem dependent on changes in blood fat levels, but instead on risk status. Although high cardiovascular risk patients were specifically selected for this study based on elevated baseline triglyceride levels, the benefits of this pure EPA fish oil investigational product accrued to patients regardless of their triglyceride levels. It seems that residual high cardiovascular risk itself is the marker of who may benefit from this intervention, which now may be added to the "cardiac cocktail" of therapies doctors use in high-risk patients.
Why were these results at odds with all the prior studies? The fish oil formulation used in this trial is truly unique in that it is a pure EPA compound with no DHA whatsoever. Its manufacturing is rigorous in that the pharmaceutical formulation and capsules are purified and created in a pure nitrogen, i.e., no oxygen, environment. Thus, the oxidation that plagues other fish oils is not a problem.
The fish oil nutriceutical industry is already trying to claim cardiovascular benefits of the REDUCE-IT compound by conflating those bespoke results to fish oils in general, i.e., their products. Don’t buy into it. Just like the statin data in late 1980s, it may take a while for doctors and the insurance companies to get the complete implications of the REDUCE-IT study results, but when they do and understand the rigorous scientific methods used to achieve this result, I suspect that pure EPA fish oils may be part of the strategy to optimize outcomes in high-risk cardiovascular patients. Just don’t confuse off-the-shelf fish oils with the prescription only pharmaceutical grade pure EPA product used in this seminal study. As healthcare providers will learn, the details of the science here are important, and their at-risk patients will benefit.
Dr. Loh is a board-certified internist & subspecialty-certified Cardiac specialist with an emphasis on Preventive Cardiology. He founded & directs the Ventura Heart Institute, which conducts education, research & preventive cardiovascular programs.
This article was previously published on LinkedIn.
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