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

William S. Harris, David Leonard, Nina B. Radford, Carolyn E. Barlow, Morgan R. Steele, Stephen W. Farrell, Andjelka Pavlovic, Benjamin L. Willis, Laura F. DeFina

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Background: The effects of fish oil products containing docosahexaenoic acid (DHA) on LDL-C levels are controversial. Objective: To determine if changes in erythrocyte DHA are associated with changes in LDL-C levels. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)212-217
Number of pages6
JournalJournal of clinical lipidology
Issue number1
StatePublished - Jan 1 2021
Externally publishedYes


  • Cardiovascular disease
  • Docosapentaenoic acid
  • Eicosapentaenoic acid
  • Low density lipoprotein
  • Omega-3 fatty acids
  • Prospective cohort study

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Cardiology and Cardiovascular Medicine


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