NIHR Signal Fish oil supplements do not reduce cardiovascular deaths in people with diabetes without existing vascular disease
Published on 4 December 2018
Omega-3 fatty acid supplements make no difference to cardiovascular outcomes in people with diabetes but without established cardiovascular disease. Serious vascular events like heart attack, stroke or deaths from these occurred in about 10% of people regardless of whether they took daily omega-3 or placebo capsules for seven years.
The ASCEND study is a large UK trial assessing primary cardiovascular prevention for people with any type of diabetes. A companion publication assesses the use of aspirin.
The results are consistent with a recent large Cochrane review assessing omega-3 fatty acids in any population. Pooled analysis of around 40 high-quality trials of omega-3 supplements similarly found no effect on cardiovascular events or mortality.
The finding supports NICE recommendations that omega-3 fatty acids should not be offered to people with diabetes for the prevention of cardiovascular disease.
- Cardiovascular system disorders, Diabetes, Medicines, Obesity and nutrition
Why was this study needed?
Cardiovascular disease accounted for 152,465 deaths in the UK in 2016. Around 4 million people have diabetes, mostly type 2. Adults with diabetes are two to three times more likely to develop cardiovascular disease, and nearly twice as likely to die from heart disease or stroke as those without diabetes.
Observational studies have suggested that consumption of oily fish, which is high in omega-3 fatty acids, reduces risk of heart disease. However, randomised controlled trials of omega-3 supplements have had conflicting results: some suggesting they prevent vascular events and others finding no effect.
The current ASCEND study assessed the effect of daily omega-3 supplements as part of primary prevention in people with diabetes who have no history of cardiovascular disease. A companion publication assesses the effect of aspirin in the same population.
What did this study do?
The ASCEND randomised controlled trial included 15,480 UK adults, aged 40 years or over, with any type of diabetes but without known cardiovascular disease. They were assigned to receive daily capsules containing 1g omega-3 fatty acid or matching olive oil placebo. They were also assigned to receive either 100 mg daily aspirin or placebo, the results of which are reported in a companion publication.
Neither participants nor researchers were aware of group allocation. Baseline characteristics and adherence to treatment were equivalent in both groups. Average follow-up was 7.4 years and complete for all participants. The trial had sufficient size to detect a 15% difference in the main outcome of a first serious vascular event, defined as non-fatal heart attack or stroke, transient ischemic attack, or death from vascular cause.
The use of olive oil as placebo is a potential limitation as this may not be a biologically inactive comparator.
What did it find?
- Omega-3 supplements made no difference to the risk of serious vascular events which occurred in 8.9% compared with 9.2% of the placebo group (rate ratio [RR] 0.97, 95% confidence interval [CI] 0.87 to 1.08).
- There was also no difference between groups when including revascularisation procedures in the outcomes along with serious vascular events: 11.4% with omega-3 vs 11.5% with placebo (RR 1.00, 95% CI 0.91 to 1.09).
- Mortality from any cause was also similar in both groups: 9.7% omega-3 vs 10.2% placebo (RR 0.95, 95% CI 0.86 to 1.05).
- Exploratory analysis revealed no effect of baseline characteristics or use of aspirin.
- There was no difference in cancer rates between groups, overall or by type.
What does current guidance say on this issue?
The NICE guideline on cardiovascular disease risk assessment and reduction states that omega-3 fatty acids should not be offered to people with diabetes; nor should they be offered for anyone as part of primary or secondary prevention. NICE advises that health professionals tell patients that there is no evidence that omega-3 compounds help to prevent cardiovascular disease.
NICE does advise that people at high cardiovascular risk and those with diabetes, specifically, eat a portion of oily fish per week and increase their intake of monounsaturated fats.
What are the implications?
Combined with the recent Cochrane review these findings seem to overwhelmingly support the current position that omega-3 supplements should not be offered to people with diabetes – either for primary or secondary prevention.
This large trial will help people with diabetes and their advisors understand the evidence-base for fish oil capsules. There is no evidence that they give cardiovascular protection.
People can continue to consume or eat polyunsaturated, monounsaturated oils and oily fish as part of a healthy balanced diet.
Citation and Funding
ASCEND Study Collaborative Group. Effects of n-3 fatty acid supplements in diabetes mellitus. N Engl J Med. 2018;379:1540-50.
This project was funded by the British Heart Foundation. Solvay, Abbott, and Mylan provided the n−3 fatty acid and placebo capsules and some funding for packaging. The aspirin and matching placebo were provided by Bayer (Germany).
Abdelhamid AS, Brown TJ, Brainard JS et al. Omega‐3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2018;(7):CD003177.
ASCEND Study Collaborative Group. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med. 2018;379:1529-39.
British Heart Foundation. Heart and circulatory diseases statistics 2018. London: British Heart Foundation; 2018.
NICE. Cardiovascular disease: risk assessment and reduction, including lipid modification. CG181. London. National Institute for Health and Care Excellence; 2014 (updated 2016).
NICE. Type 2 diabetes in adults: management. NG28. London: National Institute for Health and Care Excellence; 2015 (updated 2017).
Rimm EB, Appel LJ, Chiuve SE et al. Seafood long-chain n-3 polyunsaturated fatty acids and cardiovascular disease. A Science Advisory from the American Heart Association. Circulation. 2018;138:e35–47.
Siscovick DS, Barringer TA, Fretts AM et al. Omega-3 polyunsaturated fatty acid (fish oil) supplementation and the prevention of clinical cardiovascular disease. A Science Advisory from the American Heart Association. Circulation. 2017;135(15):e867–84.
These results support data from a recent meta-analysis of 10 long-term, randomised trials showing no benefit of treatment on cardiovascular disease. The evidence, therefore, supports current clinical practice guidelines, stating that n-3 marine fatty acids should not be prescribed for patients at risk of cardiovascular disease.
Is there any remaining uncertainty? Although there is robust evidence that 1g/day is ineffective, this dose is only about 25% of that required to lower blood concentrations of liver-derived triglyceride-rich lipoproteins which can contribute to the development of cardiovascular disease.
However, whether these much higher doses have any effect on cardiovascular disease remains uncertain.
Chris D Byrne, Professor of Endocrinology and Metabolism, University of Southampton
The commentator declares no conflicting interests