Highlights
- •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.
Abstract
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.
Graphical abstract
Graphical Abstract
Keywords
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References
- Inflammatory gene expression in whole blood cells after EPA vs. DHA supplementation: results from the ComparED study.Atherosclerosis. 2017; 257: 116-122
- Regulation of lipid metabolism-related gene expression in whole blood cells of normo- and dyslipidemic men after fish oil supplementation.Lipids Health Dis. 2012; 11: 172
- Advances in our understanding of oxylipins derived from dietary PUFAs.Adv Nutr. 2015; 6: 513-540
- Associations of omega-3 fatty acid supplement use with cardiovascular disease risks: meta-analysis of 10 trials involving 77917 individuals.JAMA Cardiol. 2018; 3: 225-234
- Marine omega-3 supplementation and cardiovascular disease: an updated meta-analysis of 13 randomized controlled trials involving 127 477 participants.J Am Heart Assoc. 2019; 8: e013543
- Marine n-3 fatty acids and prevention of cardiovascular disease and cancer.N Engl J Med. 2019; 380: 23-32
- Fish oils and plasma lipid and lipoprotein metabolism in humans: a critical review.J Lipid Res. 1989; 30: 785-807
- Safety and efficacy of Omacor in severe hypertriglyceridemia.J Cardiovasc Risk. 1997; 4: 385-392
- Correlation of serum triglyceride and its reduction by omega-3 fatty acids with lipid transfer activity and the neutral lipid compositions of high-density and low-density lipoproteins.Atherosclerosis. 1999; 143: 285-297
- Omega-3 free fatty acids for the treatment of severe hypertriglyceridemia: the EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial.J Clin Lipidol. 2014; 8: 94-106
- Fenofibrate for the treatment of type IV and V hyperlipoproteinemias: a double-blind, placebo-controlled multicenter US study.Clin Ther. 1989; 11: 69-83
- Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] trial).Am J Cardiol. 2011; 108: 682-690
- Effects of eicosapentaenoic acid versus docosahexaenoic acid on serum lipids: a systematic review and meta-analysis.Curr Atheroscler Rep. 2011; 13: 474-483
- Extended-release niacin vs gemfibrozil for the treatment of low levels of high-density lipoprotein cholesterol. Niaspan-Gemfibrozil Study Group.Arch Intern Med. 2000; 160: 1177-1184
- Omega-3 fatty acids for the management of hypertriglyceridemia: a science advisory from the American heart association.Circulation. 2019; 140: e673-e691
- Usefulness of icosapent ethyl (eicosapentaenoic acid ethyl ester) in women to lower triglyceride levels (results from the MARINE and ANCHOR trials).Am J Cardiol. 2017; 119: 397-403
- Icosapent ethyl for the treatment of hypertriglyceridemia.Expert Opin Pharmacother. 2013; 14: 1409-1416
- Prescription omega-3 fatty acid products containing highly purified eicosapentaenoic acid (EPA).Lipids Health Dis. 2017; 16: 23
- The Omega-3 Index: a new risk factor for death from coronary heart disease?.Prev Med. 2004; 39: 212-220
- The omega-3 index: clinical utility for therapeutic intervention.Curr Cardiol Rep. 2010; 12: 503-508
- The Omega-3 Index and relative risk for coronary heart disease mortality: estimation from 10 cohort studies.Atherosclerosis. 2017; 262: 51-54
- Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study).Am J Cardiol. 2012; 110: 984-992
- Eicosapentaenoic acid and docosahexaenoic acid containing supplements modulate risk factors for cardiovascular disease: a meta-analysis of randomised placebo-control human clinical trials.J Hum Nutr Diet. 2018; 31: 67-84
- Omega-3 polyunsaturated fatty acids favourably modulate cardiometabolic biomarkers in type 2 diabetes: a meta-analysis and meta-regression of randomized controlled trials.Cardiovasc Diabetol. 2018; 17: 98
- Efficacy and safety of TAK-085 compared with eicosapentaenoic acid in Japanese subjects with hypertriglyceridemia undergoing lifestyle modification: the omega-3 fatty acids randomized double-blind (ORD) study.J Clin Lipidol. 2013; 7: 199-207
- Long-term comparison of ethyl icosapentate vs. Omega-3-Acid ethyl in patients with cardiovascular disease and hypertriglyceridemia (DEFAT trial).Circ J. 2019; 83: 1368-1376
- Influence of omega-3 polyunsaturated fatty acid-supplementation on platelet aggregation in humans: a meta-analysis of randomized controlled trials.Atherosclerosis. 2013; 226: 328-334
- Effect of fish oil supplementation on fasting vascular endothelial function in humans: a meta-analysis of randomized controlled trials.PLoS One. 2012; 7: e46028
- The relation of red blood cell fatty acids with vascular stiffness, cardiac structure and left ventricular function: the Framingham Heart Study.Vasc Med. 2015; 20: 5-13
Article info
Publication history
Published online: December 08, 2020
Accepted:
November 30,
2020
Received in revised form:
November 3,
2020
Received:
September 1,
2020
Footnotes
Funding: The Cooper Institute, a 501(c)(3) nonprofit research institute, provided internal funding for this study.
Authors' contribution: Authors' contributions: NBR and WSH developed the research question and WSH wrote the article. DL performed statistical analysis and edited the article. CEB summarized the data and edited the article. NBR, MS, AP, BLW and LFD provided critical clinical input and edited the article.
Disclosures: WSH is the President of OmegaQuant Analytics, LLC, a laboratory that performed the omega-3 blood testing for this study. The other authors have no conflict of interest to declare in relation to the preparation and submission of this article.
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