It's Looking Bad for Fish Oil and CVD

Fish oil supplements and cardiovascular disease 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 confused the public.

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 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:

  • 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 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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