Dr Murray busts fishy study.

April 18, 2006

Conspiracy, bias, or just plain stupidity? Part II. (From Natural Living Newsletter) Introduction In a previous newsletter, I broached the subject that there appears to be something “fishy” about the portrayal of natural products in the major medical journals. I questioned whether the major medical journals are truly presenting accurate information and pointed out that even the editors or former editors of prestigious journals like the Lancet, New England Journal of Medicine, and British Medical are simply extensions of the marketing departments of major drug companies. Previously, a review published in the Journal of the American Medical Association estimated that 95% of medical studies in the most prestigious

journals contain false or misleading statistics. To illustrate the nature of the problem, let’s take a look at the most recent “negative” review of fish oils against cardiovascular mortality. In case you missed it, in early April 2006 the media headlines claimed “Fish oil Supplements have no Effect on Heart Disease or Cancer.” The source of these false statements was a review article published in BMJ (British Medical Journal).1 What the study concluded and what the media grabbed a hold of was that the “Long chain and shorter chain omega 3 fats do not have a clear effect on total mortality, combined cardiovascular events, or cancer.” That is far different than saying that

they do not have benefit. So, what is the truth behind the headline? Read on. But, before you do I want to stress here first is that the use of a high quality fish oil supplement is one of the most important tools in the prevention and treatment of many diseases. That fact is irrefutable based upon a large body of clinical evidence from double-blind, placebo-controlled trials. What did the Study Really Say? According to the lead author of the study, Dr. Lee Hooper: “We did not report that ‘long chain omega-3 does not offer any protection from heart disease’, that ‘omega-3 fats have no effect on total mortality, combined cardiovascular events, or cancer’ or that omega 3 fats are of ‘no benefit’ - this is not what we found, or what we reported (despite our being misquoted in much of the press).”2 That is very interesting. So, what Dr. Hooper and his group actually found by looking at the data was that omega-3 fatty acid intake was associated with a 13% reduction on mortality. I think that finding is quite in line with what one might expect. While long-chain omega-3 fatty acids from fish oils clearly reduce the risk for heart attacks and strokes (previous reports show somewhere between 25-40%),3-5 it is highly unlikely that they would impact other causes of mortality. Therefore, when selecting total mortality as the study’s endpoint we need to make some adjustments. For example, given that heart attacks and strokes would account for between one-quarter to one-half of all deaths in the populations studied it would be expected that long-chain omega-3 fatty acid intake would reduce total mortality somewhere between 6% (25% reduction x 25% heart attack and stroke deaths) to 20% (40% reduction x 50% CHD deaths), or an average of 13% overall. Hey, wait a minute. That 13% reduction is exactly the same number that Dr. Hooper found in his analysis of the results from the randomized trials using fish oil supplements. Interesting, isn’t it? Some Issues with the Study First of all, the study was not a new study at all. What it was is a detailed review and meta-analysis. The authors of a meta-analysis

review the medical literature and then select published studies to include in their analysis based upon the studies meeting certain criteria. A meta-analysis is almost always fraught with methodological issues and this study was no different. One of the first issues to mention is that the biggest problem with meta-analysis type reviews is that they are often the collection of poorly designed studies. If all the studies are of high quality and well-designed, a meta-analysis can be quite helpful to illustrate statistical significance because the total number of subjects is often greatly increased. However, if the meta-analysis includes a very large poorly designed study it can tip the scales to a very wrong conclusion. That appears to be exactly what happened in this particular meta-analysis. In fact, the overall conclusion of the meta-analysis can be changed from “no benefit” to “clear benefit” simply by eliminating one flawed study (DART-2). This study should

not have been included in the first place because of its poor methodological quality. I am not making that judgment. TheU.S. Department of Health and Human Services’ Evidence Report from 2005 states that this study is of very poor methodology.7 One of the biggest problems with the study was that the dietary instructions were only given at the start of the 9-year study and again after 6 months. Lack of compliance was obviously a huge problem. The study failed to demonstrate compliance in 98% of the subjects. Again, if this study is excluded (as it should have been) the results are also changed from “no benefit” to “clear benefit.” Clearly, the results of the well-designed studies show

considerable benefits from a higher intake of the long-chain omega-3 fatty acids from fish oils. Another huge problem with the meta-analysis is that many of the studies utilized based the intake of omega-3 fatty acids upon dietary questionnaires. These sorts of food frequency questionnaires used have been sharply criticized because they are often so inaccurate. So, what should researchers use instead? Well, in evaluating the role of omega-3 fatty acids they should rely on blood measurements. For example, in one study published in the New England Journal of Medicine that measured the levels of the long-chain omega-3 fatty acids EPA and DHA in the blood it was demonstrated that these omega-3 fatty acids produced a very clear reduction in heart attacks.8 The group with the highest intake of EPA and DHA had an 80% reduced risk of a fatal heart attack compared to the group with the lowest intake. Next, I have a big issue when the effects of fish consumption are linked to the effects of the long-chain omega-3 fatty acids. Sure, fish is the best natural source of the long-chain omega-3 fatty acids, but our fish supply is also tainted with mercury, lead, pesticide residues, and other harmful compounds. Mercury has been known to increase the risk of cardiovascular disease. While fish oils may protect against heart disease, is the benefit of eating fish counteracted by a higher intake of mercury? Apparently not as results from

another study published in the New England Journal of Medicine show that while higher body levels EPA and DHA were associated with a decreased risk for heart attacks, the higher the body mercury level the greater risk of a heart attack.9 Researchers concluded that the high mercury content of fish may diminish the protective effect of fish intake against heart disease. So, it is entirely inappropriate to lump fish consumption into the analysis of the health benefits of the long-chain omega-3 fatty acids. Another mistake is pooling the data with both the long-chain omega-3 fatty acids from fish oils with the short-chain omega-3 fatty acids alpha- linolenic acid. While the data

on the beneficial effects of the long-chain omega-3 fatty acids is quite solid, for alpha- linolenic acid the evidence is less convincing and randomized controlled trials are lacking. One of the studies included in the analysis that should not have been was conducted not on fish oil, but rather a margarine containing alpha-linolenic acid (ALA) - that's the omega 3 found in flax – versus a margarine with linoleic acid (an omega-6 fatty acid).10 Again, including this study appears inappropriate and its exclusion may have changed the picture entirely. Lastly, it has been stated that “conducting a meta-analysis study on the effectiveness of omega-3 fats for mortality,

cardiovascular disease and cancer, without considering the impact of excess omega-6 fat in the diet, is akin to reviewing the efficacy of a healthy diet without factoring the effects of smoking.”11 In other words, a high omega-6 to omega-3 fatty acid ratio would counteract the impact of an increased omega-3 fatty acid intake and make the results difficult to interpret. The reason omega-6 fatty acids counteract the effects of the omega-3 fatty acids relates to the production of eicosanoids (prostaglandins, thromboxanes, and leukotrienes) from omega-6 fatty acids. Chronic excessive production eicosanoids derived from omega-6 fatty acids is associated with an increased risk heart attacks,

thrombotic stroke, arrhythmia, arthritis, osteoporosis, inflammation and cancer. The overall benefits of a higher intake of omega-3 fatty acids appears to be related to reducing the omega-6 to omega-3 fatty acid ratio and availability of omega-6 fatty acids for eicosanoid synthesis. Final Comments The bottom line is that a pharmaceutical grade fish oil supplement is one of the key foundation formulas for good health. In fact, the development of these high quality fish oil products is one of the major developments in nutritional medicine. In previous newsletters and throughout my website I have continually stressed the importance of supplementing the diet with these long-chain omega-3 fatty acids. Based upon the totality of research, in order to significantly promote health and reduce the risk for cardiovascular disease the daily dosage of EPA and DHA combined should be at least 1,000 mg per day. The specific

product that I recommend is RxOmega-3 Factors from Natural Factors. It is one of the few fish oil products that truly is a pharmaceutical grade product. Each capsule provides 400 mg of EPA and 200 mg of DHA - the exact ratio used in so many of the clinical studies. So, two capsules daily easily achieve the recommended dosage. Key references: Hooper L, Thompson RL, Harrison RA, et al. Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. BMJ. 2006;332:752-60. Hooper L, Riemersma R, Durrington P, et. Al. Authors' reply - omega 3s and health. BMJ.com April 7, 2006. He K, Song Y, Daviglus ML, Liu K, Van Horn, L, Dyer AR, Greenland P. Accumulated evidence on fish consumption and coronary heart disease mortality: a meta-analysis of cohort studies. Circulation 2004;109:2705- 11. Whelton SP, He J, Whelton PK, Muntner P. Meta-analysis of

observational studies on fish intake and coronary heart disease. Am J Cardiol 2004;93:1119-23. Bucher HC, Hengstler P, Schindler C, Meier G. N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trial. Am J Med 2002:112:298-304. 4. Burr ML, Ashfield-Watt PA, Dunstan FD, Fehily AM, Breay P, Ashton T, et al. Lack of benefit of dietary advice to men with angina: results of a controlled trial. European Journal of Clinical Nutrition 2003;57:193- 200. Burr ML, Ashfield-Watt PA, Dunstan FD, et al. Lack of benefit of dietary advice to men with angina: results of a controlled trial. Eur J Clin Nutr. 2003; 57:193-200. Effects of omega-3 fatty acids on cardiovascular disease. http://www.ahcpr.gov/clinic/epcsums/o3cardsum.htm/dec.2004 Albert CM, Campos H, Stampfer MJ, et al. Blood levels of long-chain n-3 fatty acids and the risk of sudden death. N Engl J Med. 2002;346(15):1113-8. Guallar E, Sanz-Gallardo MI,

van't Veer P, Bode P, et al. Mercury, fish oils, and the risk of myocardial infarction. N Engl J Med 2002;347:1747-54. Bemelmans WJ, Broer J, Feskens EJ, et al. Effect of an increased intake of alpha-linolenic acid and group nutritional education on cardiovascular risk factors: the Mediterranean Alpha-linolenic Enriched Groningen Dietary Intervention (MARGARIN) study. Am J Clin Nutr. 2002 Feb;75(2):221-7. Tribole EF. Excess Omega-6 Fats Thwart Health Benefits from Omega-3 Fats. BMJ.com March 27, 2006. We respect your online privacy. If you prefer not to receive any further e-mails from us, please click

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