Well, this is a massive disappointment.
As some of you will know, I've long thought that the evidence was strongly in favor of the view that alpha-linolenic acid (short-chain, plant-derived omega-3; ALA) is as effective as EPA and DHA (fish oil) at protecting the heart. Unfortunately, while there is lots of evidence on one or the other, there is very little head-to-head comparisong in a single study, and design features in those studies tend to make strong reliance on them unwise.
A couple of years ago, I started seeing refs to the ongoing Alpha Omega Trial, which was designed to be just what is needed: a single, direct trial of outcomes in heart attack patients which was designed to be just what is needed: a single, direct trial of outcomes in heart attack patients (alas, a clinical trial in perfectly healthy people will never happen: it would take decades to run, wouldn't have as strong an economic payoff, and would cost an absurd amount of money) given either EPA+DHA, ALA, both together, or placebo (all delivered in a very low-trans-fat margarine).
Well, the darned thing has just been published, and they got no significant protective effect from ANY of the interventions:
Why does this contrast with most previous evidence on the subject? I think it's pretty obviously because of a critical design element of which I had been previously unaware: ALL patients in the trial "were receiving state-of-the-art antihypertensive, antithrombotic, and lipid-modifying therapy"(1)!
Obviously, when you have patients that are already as well-managed as the medical system can do, using meds that do some of the same things that n3 does to protect the heart, you're going to minimize the benefit. This result is unsurprising; what's surprising is that they designed the thing this way in the first place.
So we learn essentially nothing, except that after you've already gone to the trouble of getting heart patients to take drugs to control their blood pressure, lower their lipids (and in most cases inflammation), and thin their blood, it's not worth the time and expense to ALSO get them to start eating more omega-3 fatty acids.
No, I do not think that this was a Vast Pharmaceutical Industry Conspiracy Against Supplements. Rather, I imagine that this was done because of some kind of misguided "ethical" concern, where they didn't want to "deny" patients the best that we already know we can do for them in order to set them up as guinea pigs for omega-3s. But omega-3s are cheaper, safer, easier to administer, and there is nowhere near the profit motive required for robust funding as their is for patentable drugs (tho' they did get suppport in the form of "Margarine development, production and distribution" from Unilever, who of course makes this kind of product).
What academic and public-health funding and scientists are uniquely equipped to do is to test omega-3s could do on their own, INSTEAD of aggressive pharmaceutical risk factor management -- or, better yet, to set them up AGAINST such a strategy in a fifth arm of the trial (or even a sixth: placebo vs. ALA vs EPA+DHA vs all 3 omegas vs pharma vs. pharma plus one or both omegas).
What a silly waste of money and opportunity.
2 additional findings, suggestive but not robust enough to rely on:
Patients with diabetes who have had a myocardial infarction are particularly prone to ventricular arrhythmias and sudden death. In a post hoc, exploratory analysis of data from these diabetic patients, we found reductions in cardiovascular end points with EPA–DHA, as compared with placebo, that were in line with those shown in the GISSI Prevenzione trial. The strongest effects — reductions of approximately 50% — were the effects on the rates of fatal coronary heart disease and arrhythmia-related events. The rate of arrhythmia-related events was also reduced with ALA as compared with placebo or EPA–DHA only. This finding is supported by the results of a cohort study involving women, in which ALA intake was inversely associated with the risk of sudden death. However, it is important to note that our results with respect to patients with diabetes are only hypothesis-generating and do not permit definitive conclusions to be drawn.((1) op cit)
*(PS: yes, the dosage was plenty (tho' I'd've liked a LITTLE more ALA): evidence from existing clinical trials and epidemiology are pretty clear that there is a threshold effect right around these doses with no additional, dose-dependent benefit beyond them).
1. n–3 Fatty Acids and Cardiovascular Events after Myocardial Infarction
Daan Kromhout, M.P.H., Ph.D., Erik J. Giltay, M.D., Ph.D., and Johanna M. Geleijnse, Ph.D. for the Alpha Omega Trial Group
New England Journal of Medicine; Online First, August 29, 2010 (10.1056/NEJMoa1003603)
No PMID yet
Edited by Michael, 31 August 2010 - 03:42 PM.