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Meta-Analysis
. 2024 Apr;99(4):534-541.
doi: 10.1016/j.mayocp.2023.11.026. Epub 2024 Mar 20.

Circulating Docosahexaenoic Acid and Risk of All-Cause and Cause-Specific Mortality

Evan L O'Keefe  1 , James H O'Keefe  2 , Nathan L Tintle  3 , Jason Westra  4 , Luc Albuisson  5 , William S Harris  6
Affiliations
Meta-Analysis

Circulating Docosahexaenoic Acid and Risk of All-Cause and Cause-Specific Mortality

Evan L O'Keefe et al. Mayo Clin Proc. 2024 Apr.

Abstract

Objective: To assess the associations of docosahexaenoic acid (DHA), a marine omega-3 fatty acid, with long-term all-cause mortality, cardiovascular (CV) mortality, and cancer mortality.

Patients and methods: We analyzed data from UK Biobank, which included 117,702 subjects with baseline plasma DHA levels and 12.7 years of follow-up between April 2007 and December 2021. Associations with risk for mortality endpoints were analyzed categorically by quintile of DHA plasma levels.

Results: Comparing the lowest to highest quintiles of circulating levels of DHA, there was 21% lower risk of all-cause mortality (HR, 0.79; 95% CI, 0.74 to 0.85; P<.0001). In a secondary analysis, we merged the UK Biobank findings with those from a recent FORCE (Fatty Acid and Outcome Research Consortium) meta-analysis that included 17 prospective cohort studies and 42,702 individuals examining DHA and mortality associations. The cumulative sample population included 160,404 individuals and 24,342 deaths during a median of 14 years of follow-up. After multivariable adjustment for relevant risk factors comparing the lowest to the highest quintiles of DHA, there was 17% lower risk of all-cause mortality (95% CI, 0.79 to 0.87; P<.0001), 21% lower risk for CV disease mortality (95% CI, 0.73 to 0.87; P<.001), 17% lower risk for cancer mortality (95% CI, 0.77 to 0.89; P<.0001), and 15% lower risk for all other mortality (95% CI, 0.79 to 0.91; P<.001).

Conclusion: Higher DHA levels were associated with significant risk reductions in all-cause mortality, as well as reduced risks for deaths due to CV disease, cancer, and all other causes. The findings strengthen the hypothesis that DHA, a marine-sourced omega-3, may support CV health and lifespan.

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Conflict of interest statement

POTENTIAL COMPETING INTERESTS

Dr J.H. O’Keefe is the Chief Medical Officer of Cardiotabs, a nutraceutical company. Dr Harris holds stock in OmegaQuant Analytics, which offers blood fatty acid testing (including the Omega-3 Index) for researchers, clinicians, and consumers. All other authors report no potential competing interests.

Figures

FIGURE 1.
FIGURE 1.
Associations of circulating docosahexaenoic acid levels by quintile with all-cause and cause-specific mortality in the UK Biobank. The y-axis is truncated at 50% risk reduction.
FIGURE 2.
FIGURE 2.
Associations of circulating docosahexaenoic acid levels with all-cause and cause-specific mortality in the updated 18-cohort meta-analysis.
See this image and copyright information in PMC

References

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