The study, which as published on Sunday in the New England Journal of Medicine, was titled “Effects of n−3 Fatty Acid Supplements in Diabetes Mellitus,” and was a result of the ASCEND trial (A Study of Cardiovascular Events iN Diabetes). This was a study conducted between 2005 and 2011 that included 15,480 patients. The subjects, who had diabetes but no history of cardiovascular disease, were randomly assigned to fish oil supplementation (1 g daily) or a matching placebo.
The trial was conducted with British subjects at the University of Oxford. The subjects were at least 40 years of age with no upper limit. If they were taking fish oil supplements, they were asked to stop using them “wherever possible.”
The subjects were assigned to either a 1 gram capsule containing 460 mg of EPA and 380 mg of DHA or a placebo daily. The patients were mailed 6 month supplies of the capsules and filled out questionnaires at the same intervals.
The pre-specified primary efficacy outcome was the first serious vascular event. This was defined as a composite of nonfatal myocardial infarction or stroke (excluding confirmed intracranial hemorrhage), TIA (transient ischemic attack), or a measure they referred to as ‘vascular death excluding intracranial hemorrhage.’ The secondary efficacy outcome was a composite of any serious vascular event or any arterial revascularization procedure.
Conclusion: routine omega-3s supplementation not recommended
The authors concluded that on their primary measures, there was no difference between the groups.
“In conclusion, among patients with diabetes but without evidence of cardiovascular disease at baseline, there was no significant difference in the incidence of serious vascular events between those who received n−3 fatty acids and those who received placebo. These findings, together with results of earlier randomized trials involving patients with and those without diabetes, do not support the current recommendations for routine dietary supplementation with n−3 fatty acids to prevent vascular events,” the authors wrote.
The reaction of industry groups and nutritional lipids experts focused on three areas: At least one result of the trial was positive, but was downplayed; the dosage used for a patient population like this was probably too low; and the baseline omega-3 levels of this group also appeared to be already strangely high.
Were test subjects already doing the right things?
Prof. William Harris, PhD, one of the world’s foremost experts on omega-3s, is a principle in the testing firm OmegaQuant. Harris was hired by the authors to run blood samples. Harris noted that the subjects he tested were strangely high on their Omega 3 Index levels.
“We did about 1% of the study population. We tested 150 subjects at baseline and at some point in the follow up. We found that the treatment group had a 7% Omega 3 Index at baseline, which was already quite high,” Harris told NutraIngredients-USA.
“That’s close to what we would consider the basement level—8%—for a protective effect. So you are in effect looking for the omega-3 intervention to have an additional effect on top of that,” Harris said.
The Global Organization of EPA and DHA Omega-3s (GOED) also concurred, noting that for unexplained reasons, the study population was not representative of the UK population as a whole.
“These patients are very different from the general adult UK population, for whom the average omega-3 index is less than 4%. While omega-3 treatment increased the Omega-3 Index to 9.1%, the high baseline Omega-3 Index suggests that the study participants were already close to the range of omega-3 index (8-12%) that is optimal for cardiovascular prevention, so it is to be expected that an additional dose of omega-3 would only have a modest effect,” the group said in a statement.
Vascular deaths fewer in test group
Harris also noted that there was a positive outcome in the study, which was downplayed in the final conclusion.
“In the main paper, in Table 4, Vascular Death is the sum of coronary death, stroke death and ‘other’ vascular causes of death. I suppose that could include things like a ruptured aortic aneurism. There were 196 vascular deaths in the omega-3s group and 240 in the placebo group. This was a statistically significant difference. This was also one of the pre-defined primary endpoints, so not an ‘exploratory’ or ‘fishing for positive p-values’ type finding,” Harris said.
Standard diet could have skewed results
Duffy MacKay, ND, senior vice president of scientific and regulatory affairs for the Council for Responsible Nutrition, said the study is a high quality one, so the results must be taken seriously.
“This is a very robust and rigorous trial published in a major journal,” MacKay said. “It was almost seven years long, so the authors are to be commended for that.”
“But I do question the idea that it’s only the omega-3s that count. The amount of omega-6 is important, too, and getting the right ratio between omega-3 and omega-6 in the diet. We know the modern diet, whether in the US or the UK, is too high in omega-6 for optimum heart health,” he said.
“Giving the one capsule as they did, you are going to get high compliance. But you may need more omega-3s to have a benefit if you are consuming the standard diet,” MacKay added.
Source: New England Journal of Medicine
2018 Aug 26. doi: 10.1056/NEJMoa1804989. [Epub ahead of print]
“Effects of n-3 Fatty Acid Supplements in Diabetes Mellitus.”
Authors: ASCEND Study Collaborative Group