A trial of omega-3 fatty acid supplements showed they have little or no effect on the risk of cancer or cardiovascular disease in the general population. The finding contradicts the widespread belief that these supplements at usual doses protect the heart.
A large trial of 25,871 men and women in the United States compared the impact of taking about 1g a day of omega-3 fatty acid supplements with placebo on major cardiovascular events and invasive cancer. The results are consistent with a recent large Cochrane review assessing omega-3 fatty acids.
The trial provides fresh evidence to support current recommendations that omega-3 fatty acid supplements in usual doses should not be offered for the prevention of cardiovascular disease. It also provides new evidence that they do not reduce the risk of cancer. This may not be the end of the story though as other research into other doses exists.
Why was this study needed?
There are approximately 152,000 deaths from cardiovascular disease in the UK each year and 164,000 cancer deaths. The combined annual healthcare costs of these diseases total around £18.4 billion.
Several observational studies have associated higher intake of omega-3 fatty acids with reduced risks of cardiovascular disease and cancer. However, trials testing the effect of various doses of omega-3 fatty acid supplementation on cardiovascular disease outcomes or cancer risk have shown inconsistent results.
The VITAL randomised controlled trial was conducted to address this knowledge gap. It also looked at whether Vitamin D reduced either risk, though the results are reported in a separate paper.
What did this study do?
The omega-3 arm of the VITAL trial involved 12,786 men aged 50 or older and 13,085 women aged 55 or over in the United States, including 5,106 black participants. They were randomised to take omega-3 fatty acids or placebo from November 2011 to March 2014. None had cardiovascular disease or cancer at baseline.
Annual questionnaires were used to assess whether people were continuing to take the supplements, had any side effects or had developed any major illnesses up until December 2017.
Only trials of the lower daily dose of 1g omega-3 fatty acids were included, meaning dose-response relationships couldn’t be explored. This is the dose recommended for cardiovascular protection by the American Heart Association for people with a history of cardiovascular disease.
What did it find?
- Supplementation with omega-3 fatty acids did not result in a lower incidence of major cardiovascular events compared to placebo, occurring in 3% of each group (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.80 to 1.06).
- Analysis of secondary endpoints revealed a small reduction in the risk of myocardial infarction which occurred in 1.1% of the omega-3 fatty acid group compared to 1.5% of the placebo group (HR 0.72; 95% CI 0.59 to 0.90).
- Omega-3 fatty acid supplementation did not reduce cancer risk. Invasive cancer was diagnosed in 6% of each group (HR 1.03, 95% CI 0.93 to 1.13). There was no effect on the secondary end points of site-specific cancers or death from cancer.
- No excess risks of bleeding or other serious adverse events were observed.
What does current guidance say on this issue?
NICE 2016 guidance on cardiovascular disease risk states that there is no evidence that routine omega-3 fatty acid supplements help prevent cardiovascular disease.
It says that omega-3 fatty acid supplements should not be offered for primary or secondary prevention of cardiovascular disease, or to people with chronic kidney disease, type 1 or type 2 diabetes. However, people at high risk of or with existing cardiovascular disease are advised to eat at least two portions of fish each week, including a portion of oily fish, and at least four to five portions of nuts, seeds and legumes.
There is no guidance on omega-3 fatty acid supplements to prevent cancer.
What are the implications?
This large trial in an ethnically diverse population supports current NICE guidance that omega-3 supplements at this dose do not prevent cardiovascular disease. Neither should they be recommended to reduce the risk of cancer.
People should continue eating foods that are rich in omega-3, including oily fish, nuts and seeds, which are an important part of a healthy diet. Because of the remaining uncertainty about dose, this is unlikely to be the last word on this issue.
Citation and Funding
Manson JE, Cook NR, Lee IM et al; VITAL Research Group. Marine n-3 fatty acids and prevention of cardiovascular disease and cancer. N Engl J Med. 2019;380:23-32.
This study was funded by grants (U01 CA138962 and R01 CA138962) from the National Cancer Institute, the National Heart, Lung, and Blood Institute, the Office of Dietary Supplements, the National Institute of Neurological Disorders and Stroke, and the National Center for Complementary and Integrative Health.
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.
Bhatt DL, Steg PG, Miller M et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380:11-22.
Keaney JF, Rosen CJ. VITAL signs for dietary supplementation to prevent cancer and heart disease. N Engl J Med. 2019;380:91-93.
NICE. Cardiovascular disease risk assessment and reduction, including lipid modification. CG181. London: National Institute for Health and Care Excellence; 2014, updated 2016.
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