Every year American consumers spend more than $ 6 billion on pills and fortified foods that contain omega-3 fatty acids that they hope will make them healthier. But now a new, big study by researchers at McMaster University is asking questions about whether those dollars are being wasted and whether the fats that normally come from fish have any effect on heart attack prevention at all.
The study tracked 12,536 patients with high blood sugar or diabetes who had previously had heart attacks, strokes, or other heart problems. Patients were randomly selected to receive either 1 gram of purified, prescription fish oil, which contained the exact DHA and EPA subtypes of omega-3s that doctors believed would work best, or placebo.
The study showed that the 6,281 patients who received fish oil were no more or less likely to die from cardiovascular causes than the 6,255 who received a placebo. Ingesting fish oil did not result in fewer heart attacks, fewer strokes, fewer hospitalizations for heart problems, fewer stenting procedures, or less chest pain.
Patients were also randomly selected to receive one of two versions of insulin, one from Sanofi, which funded the study. Taking the Sanofi insulin did not prevent heart problems either, but it did lead to fewer patients suffering from diabetes. The results will be published today in the New England Journal of Medicine and presented at the American Diabetes Association’s annual meeting in Philadelphia.
Jackie Bosch of McMaster University, the study’s lead investigator, said she was “surprised” by the result, but said a closer look at the data showed surprising consistency. “The effect, if any, is likely to be small,” she says, and in people in the early stages of diabetes, the fish oil does not appear to help prevent heart problems. “If you’re looking to spend money on supplements, buy fish instead,” she says. “Maybe it prevents us from eating the other bad things.”
It could be that omega-3 supplements just aren’t strong enough to make a big difference in a clinical trial, says James Stein of the University of Wisconsin, Madison. Treatment would need to be “consistently effective” to reduce the risk of heart attack in patients who have not had just one. “Omega-3 supplements,” he says, “are just not that strong.”
Steven Nissen, chairman of cardiology at Cleveland Clinic and co-author of Heart411, a book about heart disease, goes even further. “I’m not shocked at all,” he says, arguing that existing clinical studies pointing to the benefits for the products have been “sloppy” and “not up to rigorous standards.”
This clinical study is not the last word on whether omega-3s can help the heart. The dose was only a quarter of the normal prescription dose of four grams of fish oil. It is possible that the benefit will be greater in other types of patients, who are either sicker, healthier, or simply different. The study also had nothing to say about the benefits of omega-3 fats in other parts of the body such as the brain or their use in infant formula, which is the largest source of omega-3 sales.
However, if doctors and patients become skeptical of the benefits of fish oil and other omega-3 sources such as plants, krill, and algae, the financial impact would be enormous, running into billions of dollars.
The current prescription fish oil pill is made by ProNova BioPharma. In the US, it is sold by GlaxoSmithKline under the name Lovaza, where it had sales of $ 916 million last year. Elsewhere it is sold by Abbott Laboratories. The drug is approved for reducing triglycerides in the blood in much higher doses than the study approved and is not approved for the prevention of heart problems. ProNova is issuing a press release indicating this and which I have included on the next page.
Sales of over-the-counter fish oil supplements reached $ 1.1 billion in 2010, up 11%, according to the Nutrition Business Journal. Vegetable oil supplements generated an additional $ 270 million.
The largest category of omega-3 products are not drugs or supplements, but foods like milk, bread, and cereals to which the oils have been added. The global omega-3 food market is worth $ 25 billion, according to Packaged Facts, an industry newsletter. But 40% of that is for baby food. In the USA alone, food and beverages generated annual sales of around 4 billion US dollars.
Companies are also rushing to develop new omega-3 products. Amarin, a biotechnology company, is developing a new fish oil pill to compete with Lovaza and has a market cap of $ 1.6 billion. Monsanto has developed a genetically modified soybean that contains the EPA fish oil. Such new products would be at risk if future fish oil studies were negative.
This isn’t the first study to question the benefits of omega-3 supplements. A May analysis in the Archives of Internal Medicine summarized the results of clinical studies with fish oil and came to a similar conclusion. Including a 4,837 patient study published in the New England Journal in 2010.
However, many doctors and researchers firmly believed in the effectiveness of omega-3s as a heart medicine, especially when it contained high levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) precisely because they appeared to have benefits in large clinical trials. The GISSI-Prevenzione study, an 11,000-person study from 1999, found that either consuming fish or taking supplements reduced deaths and heart attacks. A 19,000 patient study of EPA pills from Japan also appeared to show a benefit. In 2008, a study of 7,000 patients in people with heart failure appeared to show that 1 gram of fish oil reduced the risk of death. (See my previous, bubbly coverage here.)
Could these older studies just be wrong? Nissen from the Cleveland Clinic suspects that. In the first two studies, patients and doctors knew whether or not they were getting extra fish and fish oil, which may bias the results. In the third case, an unusual statistical adjustment was made. He also suspects that researchers who conducted studies that found no benefit may not have published them.
There are other options as well. In the New England Journal, the researchers give four. People with diabetes may be different from other patients. It could be that the participants in this study ate enough fish that they didn’t need fish oil pills. or it could be that they were just taking better heart medications, including aspirin, ACE inhibitors, beta blockers, and cholesterol-lowering statins, and that the fish oil had less of an effect.
It could also be that patients in previous studies benefited because they started taking omega-3 pills within three months of a heart attack or if they had heart failure, a condition in which the heart is weak. At that moment, patients were at high risk of arrhythmias, irregular heart rhythms that could be fatal – something known as sudden cardiac death. The omega-3 may work by preventing them.
Stein, the Wisconsin cardiologist, says he “strongly suspects” that preventing sudden cardiac death was what made the previous studies so positive. However, for most patients, this is not a reason to use them.
“Low-dose fish oil supplements – such as vitamin E, folic acid, B vitamins, and many other supplements – made biological sense, had supportive epidemiological data, and even had one or two clinical studies,” he writes. “But in 2012, cardiovascular disease prevention is unlikely to be a major issue. Patients and doctors need to stick to what really works and not put so much hope in supplements. “
Results of the ORIGIN study
Oslo, Norway, June 11, 2012: Pronova BioPharma ASA (OSE: PRON.OL) confirms information released today by Sanofi, derived from the ORIGIN study, a clinical cardiovascular intervention study in patients with pre-diabetic and early type II Diabetes that emerged did not show a significant reduction in morbidity and mortality of 1 gram / day of omega-3 ethyl acetate 90 versus placebo in patients with dysglycemia and other risk factors for cardiovascular disease.
The ORIGIN study was a diabetes study initiated and sponsored by Sanofi. It was a 6-year, multicenter, international, randomized 2×2-factorial design study in more than 12,500 patients with pre-diabetic and early type II diabetes to evaluate the effects of insulin glargine versus standard care and omega-3 ethyl esters 90 versus placebo to reduce cardiovascular morbidity and mortality.
The study population and cardiovascular disease risk profile in the ORIGIN study differed significantly from other supportive studies on Omacor that led to the currently approved therapeutic indications. The patient population in the ORIGIN study was generally at a lower risk than the populations included in the GISSI-Prevenzione (recent myocardial infarction) and GISSI-heart failure (established heart failure) studies.
In addition, ORIGIN was not designed to study the effects of triglyceride (TG) reduction on cardiovascular mortality. The patient population in the ORIGIN study had a TG value within the normal reference range. Even so, the low dose of omega-3 acid ethyl esters 90 used in the study still resulted in a small but statistically significant reduction in triglyceride levels in patients.
The current Omacor advertisements will remain unaffected. Omacor remains an approved, widely used, and effective treatment for hypertriglyceridemia and in post-MI patients.
The data from the study was presented today at the American Diabetes Association (ADA) 72nd Scientific Session, June 8-12, 2012 in Philadelphia, PA, USA, and published in the New England Journal of Medicine.
For further information please contact:
Gøran Gannedahl, VP R & D & MRA Tel .: +47 91 55 26 26
This information is subject to disclosure requirements under Section 5-12 of the Norwegian Securities Trading Act.