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n-3 PUFA Esterified to Glycerol or as Ethyl Esters Reduce Non-Fasting Plasma Triacylglycerol in Subjects with Hypertriglyceridemia: A Randomized Trial

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Lipids

Abstract

To date, treatment of hypertriglyceridemia with long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) has been investigated solely in fasting and postprandial subjects. However, non-fasting triacylglycerols are more strongly associated with risk of cardiovascular disease. The objective of this study was to investigate the effect of long-chain n-3 PUFA on non-fasting triacylglycerol levels and to compare the effects of n-3 PUFA formulated as acylglycerol (AG-PUFA) or ethyl esters (EE-PUFA). The study was a double-blinded randomized placebo-controlled interventional trial, and included 120 subjects with non-fasting plasma triacylglycerol levels of 1.7–5.65 mmol/L (150–500 mg/dL). The participants received approximately 3 g/day of AG-PUFA, EE-PUFA, or placebo for a period of eight weeks. The levels of non-fasting plasma triacylglycerols decreased 28 % in the AG-PUFA group and 22 % in the EE-PUFA group (P < 0.001 vs. placebo), with no significant difference between the two groups. The triacylglycerol lowering effect was evident after four weeks, and was inversely correlated with the omega-3 index (EPA + DHA content in erythrocyte membranes). The omega-3 index increased 63.2 % in the AG-PUFA group and 58.5 % in the EE-PUFA group (P < 0.001). Overall, the heart rate in the AG-PUFA group decreased by three beats per minute (P = 0.045). High-density lipoprotein (HDL) cholesterol increased in the AG-PUFA group (P < 0.001). Neither total nor non-HDL cholesterol changed in any group. Lipoprotein-associated phospholipase A2 (LpPLA2) decreased in the EE-PUFA group (P = 0.001). No serious adverse events were observed. Supplementation with long-chain n-3 PUFA lowered non-fasting triacylglycerol levels, suggestive of a reduction in cardiovascular risk. Regardless of the different effects on heart rate, HDL, and LpPLA2 that were observed, compared to placebo, AG-PUFA, and EE-PUFA are equally effective in reducing non-fasting triacylglycerol levels.

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Abbreviations

AE:

Adverse events

AG:

Acylglycerol

ApoA1:

Apolipoprotein A1

ApoB:

Apolipoprotein B

BMI:

Body mass index

DHA:

Docosahexaenoic acid

EE:

Ethyl ester

EPA:

Eicosapentaenoic acid

FA:

Fatty acids

HDL-C:

High-density lipoprotein cholesterol

HgbA1c:

Glycated hemoglobin A1

ITT:

Intention-to-treat

LDL-C:

Low-density lipoprotein cholesterol

LDL-P:

LDL particle number

LpPLA2:

Lipoprotein-associated phospholipase A2

n-3 PUFA:

Omega-3 polyunsaturated fatty acids

PP:

Per protocol

PUFA:

Polyunsaturated fatty acids

QTc:

Corrected QT interval

VLDL-C:

Very-low-density lipoprotein cholesterol

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Acknowledgments

This study was funded by Marine Ingredients (Mt. Bethel, PA, USA) and the Department of Clinical Biochemistry, Copenhagen University Hospital Gentofte (Hellerup, Denmark). Some laboratory testing was donated by Health Diagnostic Laboratory, Inc. (Richmond, VA, USA). We are indebted to participants in the study for their collaboration. We thank Tove Brink-Kjær for her help in carrying out the study. The authors’ responsibilities were as follows: JD and SS for the concept, design, and implementation of the project; AH and PBS for data collection, interpretation of data, and statistical analysis; WSH and PBS for supervision of the laboratory analysis; and AH for the drafting of the manuscript. All authors read and approved the manuscript. SS has primary responsibility for the final content. Marine Ingredients, Mt. Bethel, PA, USA, provided reagents, materials, and study medication. Some laboratory testing was donated by the Department of Clinical Biochemistry, Copenhagen University Hospital Gentofte and Health Diagnostic Laboratory, Inc.

Conflict of interest

JD is scientific advisor for Marine Ingredients. WSH is an employee of Health Diagnostic Laboratory, Inc., and is President of OmegaQuant Analytics, LLC, two laboratories that offer RBC fatty acid testing. AH, PBS, and SS each declare no conflict of interest.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Copenhagen University Hospital Gentofte, Niels Andersensvej 65, 2900, Hellerup, Denmark

    Anne Hedengran, Pal B. Szecsi, Jørn Dyerberg & Steen Stender

  2. Health Diagnostic Laboratory, Inc., Richmond, VA, USA

    William S. Harris

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  1. Anne Hedengran
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  2. Pal B. Szecsi
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Correspondence to Anne Hedengran.

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Hedengran, A., Szecsi, P.B., Dyerberg, J. et al. n-3 PUFA Esterified to Glycerol or as Ethyl Esters Reduce Non-Fasting Plasma Triacylglycerol in Subjects with Hypertriglyceridemia: A Randomized Trial. Lipids 50, 165–175 (2015). https://doi.org/10.1007/s11745-014-3968-6

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