Original Article| Volume 15, ISSUE 1, P212-217, January 2021

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Increases in erythrocyte DHA are not associated with increases in LDL-cholesterol: Cooper center longitudinal study

Published:December 08, 2020DOI:


      • The effects of DHA on LDL-C are controversial.
      • We compared changes over time in erythrocyte DHA and LDL-C levels in 9253 patients.
      • Increases in DHA levels were associated with increases in fish oil supplement use.
      • Changes in DHA levels were inversely associated with changes in LDL-C.
      • We found no evidence that the use of fish oil supplements raises LDL-C.



      The effects of fish oil products containing docosahexaenoic acid (DHA) on LDL-C levels are controversial.


      To determine if changes in erythrocyte DHA are associated with changes in LDL-C levels.


      In this prospective observational study, erythrocyte DHA levels and LDL-C levels were measured in 9253 individuals who presented for at least two examinations at a medical clinic. Changes in DHA levels and the reported use of omega-3 dietary supplements were correlated with changes in LDL-C in multi-variable adjusted models including the use of LDL-C-lowering drugs.


      Mean (standard deviation) age at baseline was 52.6 (10.6) years, and the time between exams averaged 1.9 (1.4) years. As a group, erythrocyte DHA increased from 5.0% (1.3) to 5.3% (1.3) (p < 0.001), and LDL-C was not significantly changed (109 (33) to 108 (33) mg/dL, p = 0.875). However, in multivariable-adjusted models of within-participant changes, a 1% increase in erythrocyte DHA was associated with a 1.9 mg/dL reduction in LDL-C (95% confidence interval (1.6, 2.2), p < 0.001). Similar relationships were seen with changes in erythrocyte EPA and EPA + DHA. In adjusted analyses, an increased use of omega-3 supplements was associated with a significant increase in erythrocyte DHA and a decrease in LDL-C in both users and non-users of lipid-lowering drugs.


      In a predominantly male, normolipidemic, middle-aged cohort, increases in erythrocyte DHA were associated with decreases in LDL-C, and initiating fish oil supplement use did not increase LDL-C. These findings may serve to reassure individuals who, in adopting a more heart-healthy lifestyle, want to increase their omega-3 fatty acid intake.

      Graphical abstract


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