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omega 3 supplements

NIHR Signal One gram a day of omega-3 supplements does not reduce the risk of cancer or cardiovascular disease

Published on 26 March 2019

doi: 10.3310/signal-000752

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.

Share your views on the research.

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.

Bibliography

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.

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.

Bibliography

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.

Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer

Published on 13 November 2018

Manson, J. E.,Cook, N. R.,Lee, I. M.,Christen, W.,Bassuk, S. S.,Mora, S.,Gibson, H.,Albert, C. M.,Gordon, D.,Copeland, T.,D'Agostino, D.,Friedenberg, G.,Ridge, C.,Bubes, V.,Giovannucci, E. L.,Willett, W. C.,Buring, J. E.

N Engl J Med , 2018

BACKGROUND: Higher intake of marine n-3 (also called omega-3) fatty acids has been associated with reduced risks of cardiovascular disease and cancer in several observational studies. Whether supplementation with n-3 fatty acids has such effects in general populations at usual risk for these end points is unclear. METHODS: We conducted a randomized, placebo-controlled trial, with a two-by-two factorial design, of vitamin D3 (at a dose of 2000 IU per day) and marine n-3 fatty acids (at a dose of 1 g per day) in the primary prevention of cardiovascular disease and cancer among men 50 years of age or older and women 55 years of age or older in the United States. Primary end points were major cardiovascular events (a composite of myocardial infarction, stroke, or death from cardiovascular causes) and invasive cancer of any type. Secondary end points included individual components of the composite cardiovascular end point, the composite end point plus coronary revascularization (expanded composite of cardiovascular events), site-specific cancers, and death from cancer. Safety was also assessed. This article reports the results of the comparison of n-3 fatty acids with placebo. RESULTS: A total of 25,871 participants, including 5106 black participants, underwent randomization. During a median follow-up of 5.3 years, a major cardiovascular event occurred in 386 participants in the n-3 group and in 419 in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.80 to 1.06; P=0.24). Invasive cancer was diagnosed in 820 participants in the n-3 group and in 797 in the placebo group (hazard ratio, 1.03; 95% CI, 0.93 to 1.13; P=0.56). In the analyses of key secondary end points, the hazard ratios were as follows: for the expanded composite end point of cardiovascular events, 0.93 (95% CI, 0.82 to 1.04); for total myocardial infarction, 0.72 (95% CI, 0.59 to 0.90); for total stroke, 1.04 (95% CI, 0.83 to 1.31); for death from cardiovascular causes, 0.96 (95% CI, 0.76 to 1.21); and for death from cancer (341 deaths from cancer), 0.97 (95% CI, 0.79 to 1.20). In the analysis of death from any cause (978 deaths overall), the hazard ratio was 1.02 (95% CI, 0.90 to 1.15). No excess risks of bleeding or other serious adverse events were observed. CONCLUSIONS: Supplementation with n-3 fatty acids did not result in a lower incidence of major cardiovascular events or cancer than placebo. (Funded by the National Institutes of Health and others; VITAL ClinicalTrials.gov number, NCT01169259 .).

Expert commentary

In a large well-conducted study 1g of marine fish oils did not reduce cardiovascular disease in healthy individuals for the primary prevention of cardiovascular disease or cancer.

Specifically, 460mg of eicosapentaenoic acid (EPA) and 380mg of docosahexaenoic acid were included. Therefore, there is no role for routine use of low dose fish oils or omega-3 fatty acids especially of the type found in over the counter preparations. In contrast, the REDUCE-IT trial which used 4g of EPA reduced cardiovascular disease by 25% in both primary and secondary prevention among those with and without elevated triglycerides.

The benefit did not correlate with triglyceride lowering. It is likely that high dose EPA rather than fish oils reduces cardiovascular disease.

Kausik Ray, Professor of Public Health and Honorary Consultant Cardiologist, Imperial College London

The commentator declares no conflicting interests