Fish oil supplementation alters the plasma lipidomic profile and increases long-chain PUFAs of phospholipids and triglycerides in healthy subjects

Abstract

Background: While beneficial health effects of fish and fish oil consumption are well documented, the incorporation of n-3 polyunsaturated fatty acids in plasma lipid classes is not completely understood. The aim of this study was to investigate the effect of fish oil supplementation on the plasma lipidomic profile in healthy subjects.

Methodology/principal findings: In a double-blinded randomized controlled parallel-group study, healthy subjects received capsules containing either 8 g/d of fish oil (FO) (1.6 g/d EPA+DHA) (n = 16) or 8 g/d of high oleic sunflower oil (HOSO) (n = 17) for seven weeks. During the first three weeks of intervention, the subjects completed a fully controlled diet period. BMI and total serum triglycerides, total-, LDL- and HDL-cholesterol were unchanged during the intervention period. Lipidomic analyses were performed using Ultra Performance Liquid Chromatography (UPLC) coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (QTOFMS), where 568 lipids were detected and 260 identified. Both t-tests and Multi-Block Partial Least Square Regression (MBPLSR) analysis were performed for analysing differences between the intervention groups. The intervention groups were well separated by the lipidomic data after three weeks of intervention. Several lipid classes such as phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine, sphingomyelin, phosphatidylserine, phosphatidylglycerol, and triglycerides contributed strongly to this separation. Twenty-three lipids were significantly decreased (FDR<0.05) in the FO group after three weeks compared with the HOSO group, whereas fifty-one were increased including selected phospholipids and triglycerides of long-chain polyunsaturated fatty acids. After seven weeks of intervention the two intervention groups showed similar grouping.

Conclusions/significance: In healthy subjects, fish oil supplementation alters lipid metabolism and increases the proportion of phospholipids and triglycerides containing long-chain polyunsaturated fatty acids. Whether the beneficial effects of fish oil supplementation may be explained by a remodeling of the plasma lipids into phospholipids and triglycerides of long-chain polyunsaturated fatty acids needs to be further investigated.

Trial registration: ClinicalTrials.gov NCT01034423.

Conflict of interest statement

Competing Interests: Kirsti Wettre Brønner is a clinical nutritionist/Project manager in TINE SA R&D Center, Norway. The cod liver oil used in this study, TINE EPADHA OIL Oil 1200, was produced by Martitex AS, (Havnegata 17, 8400) Sortland Norway and provided by TINE SA. (At the time of the intervention) Maritex AS was a fully owned subsidiary of TINE SA. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Flow chart of the study showing subjects enrolled, lost during follow-up and number of subjects included in the statistical analysis at baseline and after three and seven weeks of fish oil supplementation.

FO group, fish oil group; HOSO, high oleic sunflower oil group; oxFO, oxidized fish oil group (not included in the present study).

Figure 2. Multi-Block Partial Least Squares Regression (MBPLSR) analysis of the data after three weeks of intervention.

First and second PLSR components of block scores of ceramides, lysoPC, lysoPE, PA, PC and PE are shown (A–F). The samples of each intervention group are presented as blue (HOSO group) or red (FO group) circles. The (un-validated) explained variances are shown on the axes.

Figure 3. Multi-Block Partial Least Squares Regression (MBPLSR) analysis of the data after three weeks of intervention.

First and second PLSR components of block scores of PG, PS, SM, TG, the sums of lipid classes and global scores are shown (A–F). The samples of each intervention group are presented as blue (HOSO group) or red (FO group) circles. The (un-validated) explained variances are shown on the axes.

Figure 4. Cross-validated explained variance in Y.

Bar plots of the validated explained variances in Y for each block and for the global model using data obtained after three weeks of intervention are presented.

Figure 5. Multi-Block Partial Least Squares Regression (MBPLSR) analysis of the data after three weeks of intervention.

Correlation loading plot for the variables contributing to the separation of the FO and the HOSO group after three weeks are shown for LycoPC, PE, PG, PS and SM. The (un-validated) explained variances in X and Y are shown on the axes.

Figure 6. Multi-Block Partial Least Squares Regression (MBPLSR) analysis of the data after three weeks of intervention.

Correlation loading plot for the variables contributing to the separation of the FO and the HOSO group after three weeks are shown for TG and PC. The (un-validated) explained variances in X and Y are shown on the axes.