Sigh … we’ve been here before.
A Korean team reviewed the evidence from selected clinical trials, and concluded that it’s “insufficient” to prove the presumed cardiovascular benefits of omega-3s from fish.
To researchers familiar with the evidence, this misleading study is a dismaying example of – as Yogi Berra might say – “déjà vu all over again.”
It’s not as though the Koreans claimed the Earth is flat … but the shortcomings of their review tempt us to draw that analogy.
Unfortunately, they excluded major clinical trials with positive outcomes and relied heavily on small, short-duration trials with people already taking heart drugs.
When we say we’ve been here before, we can point to similarly flawed reports that didn’t stand up to scrutiny.
For example, see “Media Misreports Omega-3 Heart Study,” “New Evidence Analysis Supports Omega-3 Heart Benefits,” and “Experts Find New Fish-and-Health Review Deeply Distorting.”
As the Korean team admits, their conclusions are contradicted by those arrived at in earlier evidence reviews: “… the main findings herein are not consistent with those of the meta-analyses published before 2010” (Kwak SM et al. 2012).
And as they acknowledged, “… our findings are limited to … patients with a history of CVD [cardiovascular disease], not in healthy individuals” (Kwak SM et al. 2012).
The Korean’s review was immediately critiqued by two prominent public health researchers … Frank B. Hu, M.D., Ph.D., and JoAnn E. Manson, M.D., DrPH, from Harvard University (see “Harvard analysis finds fatal flaws”, below).
First we’ll summarize the Korean authors’ conclusions, and then we’ll cover the Harvard researchers’ well-informed commentary.
Koreans find no omega-3 benefits in heart patients
Scientists from several Korean institutes analyzed data from 14 randomized, double-blind, placebo-controlled trials that involved 20,485 patients with a history of cardiovascular disease (CVD).
The Korean reviewers found that omega-3 supplements did not reduce the risk of adverse cardiovascular events … including sudden cardiac death, heart attacks, congestive heart failure, and stroke.
As they wrote, “Our results showed insufficient [clinical] evidence of a secondary preventive effect of omega-3 fatty acid supplements against overall cardiovascular events among patients with a history of cardiovascular disease” (Kwak SM et al. 2012).
Harvard analysis finds fatal flaws in the Korean review
Drs. Hu and Manson set the stage for their cogent critique by characterizing the clinical evidence collected to date (Hu FB, Manson JE 2012):
“Omega-3 fatty acids are among the most extensively studied nutrients for their potential cardiovascular benefits.”
“A large body of evidence from experimental, clinical, and epidemiologic research has demonstrated the potential benefits of EPA-rich and DHA-rich fish oil on cardiovascular health.”
“In addition, consistent findings from prospective observational cohort investigations indicate that regular consumption of fatty fish (two times per week) is associated with a significantly lower risk of cardiovascular death.”
This record explains why the American Heart Association and public health authorities worldwide recommend eating fatty fish and/or taking fish oil supplements on a routine basis.
As the Harvard duo noted, “… almost all RCTs [randomized clinical trials] were conducted in secondary prevention settings” (Hu FB, Manson JE 2012).
In other words, most of the clinical trials conducted to date have involved people already diagnosed with and being treated for cardiovascular disease… and in the more recent trials, almost all of the participants were already taking statins and/or other heart drugs.
As the Harvard critics wrote, “… the findings from these trials have been inconsistent … which set the stage for the meta-analysis by the Korean Meta-analysis Study Group.”
Hu and Manson went on to point out the flaws in the Koreans’ evidence review (Hu FB, Manson JE 2012):
“Among 14 RCTs included in the meta-analysis, most were very small short-term studies and were not designed to evaluate CVD end points [and] disproportionally greater weights were given to these small studies.”
“In addition, the authors excluded the two large open-label trials (the GISSI-Prevenzione trial and the Japan EPA Lipid Intervention Study) that found beneficial effects of omega-3 supplementation in the primary analysis. When these trials were included in a secondary analysis, the pooled estimate for omega-3 supplementation on overall CVD events was changed to the protective direction … [and] because these two large trials … have made important contributions to the totality of the evidence, the data should not be simply ignored ...”
They went on to probe the reasons why the results of clinical trials, although generally positive, have been inconsistent (Hu FB, Manson JE 2012):
“One question that has been raised is why more recent trials (Alpha Omega, OMEGA, and SU.FOL.OM3) have not replicated significant effects of fish oil supplementation on secondary prevention of CVD that were found in earlier trials. Differences in study designs, population characteristics, and types and dosages of omega-3 fatty acids are possible explanations.”
“Most important, the newer trials were each substantially underpowered and unable to detect significant small to modest benefits on CVD outcomes because of their small sample sizes and much lower-than-expected [adverse cardiovascular] event rates.”
“Another explanation could be that the patients in the more recent trials received much better treatment with statins and antithrombotic and antihypertensive medications than those in earlier trials. The additional benefits of fish oil supplementation or any other therapy on top of … [these] cardiovascular medications are likely to be small; therefore, a much larger sample size is critical to achieve sufficient power.”
“Another important question is whether fish oil has different effects in primary and secondary prevention of CVD.” [In other words, omega-3s may prevent CVD more effectively than they can treat existing CVD … especially if a CVD patient participating in a trial testing omega-3s is already on the best available drug and diet program.]
What should doctors and patients do?
Drs. Hu and Manson posed an obvious question: “While waiting for more definitive results, what should physicians tell their patients?”
The answer they propose seems perfectly reasonable and appropriately proactive:
“To date, there is no conclusive evidence to recommend fish oil supplementation for primary or secondary prevention of CVD. However, a diet high in fatty fish (two servings of marine fish per week) should continue to be recommended for the general population and for patients with existing CVD because fish not only provides omega-3 fatty acids but also may replace less healthy protein sources, such as red meat” (Hu FB, Manson JE 2012).
And they noted that fish oil has a role to play: “For primary or secondary prevention, omega-3 supplementation cannot supersede an overall healthy diet, but a cardio-protective diet needs to be rich in omega-3 fatty acids” (Hu FB, Manson JE 2012).
We agree … the evidence that omega-3s support hearth health is just too extensive to ignore.
And, putting heart health aside, a growing body of lab and clinical evidence indicates that omega-3s from fish support optimal developmental, immune, mood, metabolic, and mental health.
Chen Q, Cheng LQ, Xiao TH, Zhang YX, Zhu M, Zhang R, Li K, Wang Y, Li Y. Effects of omega-3 fatty acid for sudden cardiac death prevention in patients with cardiovascular disease: a contemporary meta-analysis of randomized, controlled trials. Cardiovasc Drugs Ther. 2011 Jun;25(3):259-65.
Harper CR, Jacobson TA. Usefulness of omega-3 fatty acids and the prevention of coronary heart disease. Am J Cardiol. 2005 Dec 1;96(11):1521-9. Epub 2005 Oct 21.
Hu FB, Manson JE. Omega-3 Fatty Acids and Secondary Prevention of Cardiovascular Disease–Is It Just a Fish Tale?: Comment on “Efficacy of Omega-3 Fatty Acid Supplements (Eicosapentaenoic Acid and Docosahexaenoic Acid) in the Secondary Prevention of Cardiovascular Disease”. Arch Intern Med. 2012 Apr 9. [Epub ahead of print]
Kromhout D, Giltay EJ, Geleijnse JM; Alpha Omega Trial Group. n-3 fatty acids and cardiovascular events after myocardial infarction. N Engl J Med. 2010 Nov 18;363(21):2015-26. Epub 2010 Aug 28.
Kwak SM, Myung SK, Lee YJ, Seo HG; for the Korean Meta-analysis Study Group. Efficacy of Omega-3 Fatty Acid Supplements (Eicosapentaenoic Acid and Docosahexaenoic Acid) in the Secondary Prevention of Cardiovascular Disease: A Meta-analysis of Randomized, Double-blind, Placebo-Controlled Trials. Arch Intern Med. 2012 Apr 9. [Epub ahead of print]
Marik PE, Varon J. Omega-3 dietary supplements and the risk of cardiovascular events: a systematic review. Clin Cardiol. 2009 Jul;32(7):365-72. Review.
Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B, Jordan HS, Lau J. n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review. Am J Clin Nutr. 2006 Jul;84(1):5-17. Review.
Zhao YT, Chen Q, Sun YX, Li XB, Zhang P, Xu Y, Guo JH. Prevention of sudden cardiac death with omega-3 fatty acids in patients with coronary heart disease: a meta-analysis of randomized controlled trials. Ann Med. 2009;41(4):301-10.