It's Looking Bad for Fish Oil and CVD

Fish oil supplements have had a long and controversial history. There was a lot of inconsistency in the research around supplementation and several organizations only added to this confusion. The incomplete reporting by media outlets have also added to this confusion.

Here, I’ll give a brief timeline of the evidence for fish oil and CVD outcomes.

  • 1970s | A group of explorers noticed that people who consumed fish also had lower incidences of heart disease.

  • 1980s-1990s | Early observational studies also saw a connection between fish consumption and heart disease risk.

  • 1990s | A few randomized trials were conducted to see the effects of fish oil supplementation and CVD outcomes.

  • 2002 | The American Heart Association put out a statement suggesting that fish oil supplementation was beneficial for fatal outcomes.

  • 2002 - 2016 | Several randomized trials and systematic reviews found inconsistent evidence for the effects of fish oil supplementation and CVD outcomes.

  • 2016 | The American Heart Association creates a scientific advisory group to look at all the evidence and concludes that despite the controversy, there was a small benefit from fish oil and it could be worth it for people who had a history of CVD events.

  • 2018 | Large meta-analysis published in JAMA with 77,000 + participants found no statistically significant benefit from fish oil supplementation on real clinical endpoints.

Let’s look at the evidence from the recent JAMA meta-analysis.

Methods:

Primary outcomes:

  • fatal CHD

  • nonfatal heart attacks

  • stroke

  • major vascular events

  • all-cause mortality

Inclusion Criteria:

  • Must be a randomized controlled trial

  • Studies must have a minimum of 500 participants

  • Studies must be at least one year long

  • Studies must use fish oil supplements

Characteristics of Included Studies

  • 10 randomized trials included

  • 8 are double-blind, 2 are open label.

  • Has a total of 77,000+ participants

  • Average age: 64 years

  • Average length of studies: 4.4 years

  • Used mainly up to 1 g/d of fish oil (ranges: 226 to 1800 mg/day of EPA and 0 to 1700 mg/day of DHA)

Results:


Forest plot from the JAMA study of fish oil intake and cardiovascular disease events


  • No statistically significant association between fish oil supplementation and any of the primary outcomes.

  • However, the compatibility (confidence) intervals suggest very small effects.

  • Up to a 7% decrease in the rate ratio is compatible with the test model.

  • No significant differences amongst individual trials (worth remembering that these are exploratory and the analyses could be underpowered. This should not be taken as evidence for no effect.)

  • No significant associations found with subgroup analyses (same point as above)

Strengths:

  • High statistical power/increased precision for the main primary outcome

  • Only included studies of long duration

  • Included studies were mostly at low risk of bias

Limitations:

  • Used aggregated data instead of patient data

  • Did not get a chance to add data from the REDUCE-IT trial (which I cover here or the STRENGTH trial which are using much higher dosages. (3-4 g/d of EPA)

Conclusions:

Up to 1 g/d of fish oil may not have that much to offer when it comes to preventing CVD events in individuals who have a history of CVD. More research is currently underway on higher doses of fish oil supplementation, and there might be some promise there.


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