Preventive Medicine: Maybe Lazarus took fish oil

Dr. David Katz

Tales of the prowess and health effects of fish oil (or, more generically, long-chain omega-3 fatty acids) have flopped around over the years. We have been told that fish oil is all but a panacea; and we have heard it is entirely useless. But this flipping and flopping have suddenly probed whole new depths of absurdity. Within literal days of one another, two headlines appeared on Medscape, arguably the premier information portal for health care professionals, reaching diametrically opposing conclusions.

On Sept. 18, we got: “Omega 3s: Is This the Final Word?” and a commentary about the ASCEND trial telling us “the supplements had no effect on serious vascular events, cancer, or mortality.” Then, on Sept. 25, we got: “REDUCE-IT: 25 percent Reduction in MACE with High-Dose EPA.” EPA stands for eicosapentaenoic acid, one of the two major omega-3s in fish and other marine sources (the other being docosahexaenoic acid, or DHA), while MACE stands for “major adverse cardiac events.” In other words, a week after being found useless in ASCEND, omega-3s were busy preventing heart attacks, strokes, and sudden cardiac death in REDUCE-IT.

The conflicting conclusions of these two trials, one presented at the European Society for Cardiology 2018 Congress, the other at the American Heart Association Scientific Sessions 2018, are, after all, only the most recent of many. The whole, long lineage of flip-flopping conclusions warrants analysis and explanation, and that in turn requires a view from altitude.

No matter how important a nutrient, the effects it has on any given outcome over the dose range from adequate to optimal is apt to be very small. I can illustrate this. Imagine if, instead of just accepting the evidence that daily walking is good for health (which it certainly is), we decided we needed to know the active ingredient in a daily, say, 3-mile walk. Is it step 187? Step 352?

Now imagine we design trials to answer this particular question: what is the net contribution to health of step 352 on a 3-mile walk of roughly 5,300 steps? I am confident I don’t need to explain the futility of this endeavor; isolating the health contributions of step 352 would be practically impossible. But does that mean there is no health effect of step 352? Of course not! If any one step has “zero” value, then the entire walk has zero value, because (5,300 X 0) = 0. (Remember that old riddle about accepting a dollar bill with a tiny piece torn out of one corner?) And the same would be true for a 10-mile walk. So, in fact, each step must contribute something to the net health benefit of the walk. But isolating that contribution does not seem to tempt us. In the case of nutrition, for whatever reason, it not only tempts us, it actually prevails.

Because of what we may henceforth call “the step 352 problem,” I have much preferred looking at omega-3 effects across as large an expanse of evidence as possible, rather than focusing on any one trial. Doing that, as I have been obligated to, while writing editions of a nutrition textbook, I have been impressed by the diversity of such effects. While truly decisive evidence of benefit related to any one health condition has been elusive, there are strong suggestions of benefit related to cardiovascular disease, diabetes, dementia, traumatic brain injury, autoimmune disease, and more. In the aggregate, these many suggestions make a case for net health benefits from omega-3s beyond a reasonable doubt.

Accordingly, I take a daily omega-3 supplement derived from algae. Algae can provide the EPA and DHA found in fish, but is far more sustainable. Since it is possible now to eat our fish oil and have our fish (in the seas) too, why do it any other way?

The recent trials — ASCEND, and REDUCE-IT — used different doses of omega-3, and enrolled different populations. We can account for the opposing conclusions accordingly.

More importantly, however, we must account for the context in which nutrient trials are conducted, and why that context is conducive to just such conflicts. Until or unless we do so, and remediate our mishandling of science, we may expect to mourn the demise of omega-3s one week, celebrate their triumph the week following. In other words, the one reliable scientific conclusion to date appears to be that Lazarus must have been taking fish oil.