Complementary and Alternative Care/Dietary Supplements

Omega-3 Fatty Acids, Effects on Cardiovascular Disease

March 2004

Clinical Focus*

• What are the mean and median intakes of docosahexaenoic acid (DHA, 22:6 n-3), eicosapentaenoic acid (EPA, 20:5 n-3), docosapentaenoic acid (DPA, 22:5 n-3), alpha linolenic acid (ALA, 18:3 n-3), fish, fish oil, and omega-6 fatty acids, and what is the mean and median omega-6 to omega-3 fatty acid ratio, in the U.S. population?
  • Do consumption levels differ among subpopulations?
• What is the efficacy or association of omega-3 fatty acids (DHA, EPA or ALA supplements, and fish consumption) in reducing cardiovascular disease (CVD) events (including all-cause mortality, CVD mortality, non-fatal CVD events, and new diagnosis of CVD)?
• What is the efficacy or association of omega-3 fatty acids in preventing incident CVD events in people without known CVD (primary prevention) and with known CVD (secondary prevention)?
• How does the efficacy or association of omega-3 fatty acids in preventing incident CVD events differ in subpopulations, including men, premenopausal women, postmenopausal women, and different age groups?
• What are the effects of potential confounders—such as lipid levels, body mass index, blood pressure, diabetes, aspirin use, hormone replacement therapy, and cardiovascular drugs—on associations found in prospective cohort studies?
• What is the relative efficacy of omega-3 fatty acids on different CVD outcomes? Can the CVD outcomes be ordered by strength of treatment effect of omega-3 fatty acids?

Omega-3 fatty acid variables and modifier

• What is the efficacy or association of specific omega-3 fatty acids (DHA, EPA, ALA), and different ratios of omega-3 fatty acid components in dietary supplements, on CVD outcomes?
• Does the ratio of omega-6 to omega-3 fatty acid intake affect the efficacy or association of omega-3 fatty acid intake on CVD outcomes?
• How does the efficacy or association of omega-3 fatty acids on CVD outcomes differ by source (e.g., dietary fish, dietary oils, dietary plants, fish oil supplement, flax seed supplement)?
• How does the efficacy or association of omega-3 fatty acids on CVD outcomes differ by different ratios of DHA, EPA, and ALA?
• Is there a threshold or dose-response relationship between omega-3 fatty acids and CVD outcomes?
• How does the duration of intervention or exposure affect the treatment effect of omega-3 fatty acids on CVD outcomes?
• Are treatment effects or association of omega-3 fatty acids on CVD events sustained after the intervention or exposure stops?
• What is the effect or association of baseline dietary intake of omega-3 fatty acids on the efficacy of omega-3 fatty acid supplements on CVD outcomes?
• Does the use of medications for CVD and/or CVD risk factors (including lipid lowering agents and diabetes medications) affect the efficacy or association of omega-3 fatty acids?

Adverse events and drug interactions

• What adverse events related to omega-3 fatty acid dietary supplements are reported in studies of CVD outcomes and markers?
• What adverse events related to omega-3 fatty acid dietary supplements are reported specifically among diabetics and people with CVD in studies of CVD outcomes and markers?
• What interactions between omega-3 fatty acid dietary supplements and medications are reported in studies of CVD outcomes and markers?
• What interactions between omega-3 fatty acid dietary supplements and medications are reported specifically among diabetics and people with CVD in studies of CVD outcomes and markers?

*Addressed in the summary or evidence report.

Health Effects of Omega-3 Fatty Acids on Cardiovascular Disease
Summary (Publication No. 04-E009-1, March 2004)
Evidence Report (Publication No. 04-E009-2, March 2004)
(PDF Files; File Download)

EPC: Tufts-New England Medical Center
Topic Nominator: Office of Dietary Supplements, National Institutes of Health

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