A claim you hear on longevity podcasts

Does fish oil prevent heart attacks and strokes?

The claim checked: Omega-3s, even at a lower dose, cut cardiovascular events against placebo Hear it at 15:32

What do the studies say?

Leaning against

Eight of ten studies, mostly large trials and pooled analyses, found omega-3 supplements did not lower cardiovascular events; two pooled analyses found lower risk.

Computed from 10 studies that test this point, each judged by two readers, in full. 10 more studies are waiting for a full read and do not count yet.

What was said on the podcast?

“But the take-home here is that the the reduce it trial and the vital study really gold standard showing, you know, compared to placebo that if you take omega-3 fatty acids, even at a lower dose, it is reducing the cardiovascular events that occur with age.”
Rhonda Patrick, FoundMyFitness · How Omega-3s May Slow Biological Aging (New Evidence) · 15:32 on YouTube
Comes up in 4 episodes of the show.
The point checked Leaning against

Omega-3 supplementation reduces cardiovascular events vs placebo (REDUCE-IT and VITAL)

Agree 2

pooled analysis · 2019 · landmark

“In this updated meta‐analysis, we found that marine omega‐3 supplementation significantly lowered the risk of MI, total CHD, total CVD, and because of CHD or CVD, even after excluding REDUCE‐IT.”

Marine Omega-3 Supplementation and Cardiovascular Disease: An Updated Meta-Analysis of 13 Randomized Controlled Trials Involving 127 477 Participants. J Am Heart Assoc
Who: Participants of 13 large RCTs (≥500 people, ≥1 year) including ASCEND, VITAL and REDUCE-IT; mean age 64.3, 59.7% male, 39.7% diabetic
PMID 31567003

pooled analysis · 2021 · landmark

“The combined results of our meta-analysis and meta-regressions provide strong evidence of the effectiveness of EPA+DHA intake in the prevention of adverse CVD outcomes, particularly CHD events and MI.”

Effect of Omega-3 Dosage on Cardiovascular Outcomes: An Updated Meta-Analysis and Meta-Regression of Interventional Trials. Mayo Clin Proc
Who: meta-analysis of 40 randomized controlled trials of EPA/DHA supplementation (mostly high-risk or secondary prevention; VITAL and ASCEND primary prevention)
PMID 32951855

Partly agree 0

None.

Disagree 8

controlled trial · 2020 · landmark

“In this randomized clinical trial of 13 078 patients that was stopped early, daily supplementation with omega-3 fatty acids, compared with corn oil, resulted in no significant difference in a composite outcome of major adverse cardiovascular events (hazard ratio, 0.99).”

Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial. JAMA
Who: statin-treated adults at high cardiovascular risk with hypertriglyceridemia and low HDL cholesterol (mean age 62.5, 35% women, 70% diabetes) at 675 sites in 22 countries
PMID 33190147

controlled trial · 2019 · landmark

“Omega-3 fatty acid supplementation did not reduce major cardiovascular events or cancer incidence.”

Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. N Engl J Med
Who: 25,871 U.S. men aged ≥50 and women aged ≥55 without prior cardiovascular disease or cancer (primary prevention), 20% African American
PMID 30415637

controlled trial · 2010 · landmark

“In conclusion, in this trial involving patients who had had a myocardial infarction and who were receiving good clinical care, low doses of n−3 fatty acids did not significantly reduce the rates of cardiovascular end points.”

n-3 fatty acids and cardiovascular events after myocardial infarction. N Engl J Med
Who: 4837 Dutch patients aged 60-80 (78% men) with prior myocardial infarction on antihypertensive, antithrombotic and lipid-modifying therapy
PMID 20929341

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controlled trial · 2018 · landmark

“Among patients with diabetes without evidence of cardiovascular disease, there was no significant difference in the risk of serious vascular events between those who were assigned to receive n−3 fatty acid supplementation and those who were assigned to receive placebo.”

Effects of n-3 Fatty Acid Supplements in Diabetes Mellitus. N Engl J Med
Who: UK adults aged >=40 with diabetes and no atherosclerotic cardiovascular disease
PMID 30146932

pooled analysis · 2018 · landmark

“Overall, the results of this meta-analysis demonstrated no significant association of supplementation with omega-3 FAs for a mean duration of 4.4 years with the risk of fatal CHD, nonfatal MI, any CHD, or any major vascular events in the full study population and in all relevant subgroups.”

Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks: Meta-analysis of 10 Trials Involving 77 917 Individuals. JAMA Cardiol
Who: 77,917 high-risk adults (mean age 64, 61.4% men; ~66% prior CHD, 28% prior stroke, 37% diabetes) in 10 randomized trials of omega-3 FA vs placebo or open-label control
PMID 29387889

controlled trial · 2010 · landmark

“Allocation to omega 3 fatty acids was not associated with any significant effect on major vascular events (81 v 76 patients, hazard ratio 1.08 (0.79 to 1.47), P=0.64; fig 4).”

Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial. BMJ
Who: French men and women aged 45-80 with a myocardial infarction, acute coronary syndrome or ischaemic stroke in the prior 12 months
PMID 21115589

pooled analysis · 2020 · landmark

“High‐certainty evidence suggests that LCn3 intake makes little or no difference to risk of cardiovascular events.”

Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev
Who: Adults (18+) at varying cardiovascular risk, with or without existing CVD, mainly in high-income countries; RCTs lasting at least 12 months including REDUCE-IT and VITAL
PMID 32114706

pooled analysis · 2018

“Moderate- and high-quality evidence suggests that increasing EPA and DHA has little or no effect on mortality or cardiovascular health (evidence mainly from supplement trials).”

Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev
Who: Adults with or without existing cardiovascular disease, mainly in high-income countries
PMID 30019766

What else was said but not tested?

  • Even at a lower dose (VITAL, 840 mg, secondary outcomes)

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