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

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 NCT0103442

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

<p>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.</p

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.

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

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

<p>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.</p

Oxidised fish oil does not influence established markers of oxidative stress in healthy human subjects:a randomized controlled trial

Intake of fish oil reduces the risk of CHD and CHD deaths. Marine n-3 fatty acids (FA) are susceptible to oxidation, but to our knowledge, the health effects of intake of oxidised fish oil have not previously been investigated in human subjects. The aim of the present study was to investigate markers of oxidative stress, lipid peroxidation and inflammation, and the level of plasma n-3 FA after intake of oxidised fish oil. In a double-blinded randomised controlled study, healthy subjects (aged 18–50 years, n 54) were assigned into one of three groups receiving capsules containing either 8 g/d of fish oil (1·6 g/d EPA þ DHA; n 17), 8 g/d of oxidised fish oil (1·6 g/d EPA þ DHA; n 18) or 8 g/d of high-oleic sunflower oil (n 19). Fasting blood and morning spot urine samples were collected at weeks 0, 3 and 7. No significant changes between the different groups were observed with regard to urinary 8-iso-PGF2a; plasma levels of 4-hydroxy-2-hexenal, 4-hydroxy-2-nonenal and a-tocopherol; serum high sensitive C-reactive protein; or activity of antioxidant enzymes in erythrocytes. A significant increase in plasma level of EPA þ DHA was observed in both fish oil groups, but no significant difference was observed between the fish oil groups. No changes in a variety of in vivo markers of oxidative stress, lipid peroxidation or inflammation were observed after daily intake of oxidised fish oil for 3 or 7 weeks, indicating that intake of oxidised fish oil may not have unfavourable short-term effects in healthy human subject

Cross-validated explained variance in Y.

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

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

<p>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 <b>X</b> and <b>Y</b> are shown on the axes.</p

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

<p>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 <b>X</b> and <b>Y</b> are shown on the axes.</p