Abstract

PurposeReplacing saturated fatty acids (SFA) with polyunsaturated fatty acids (PUFA) is associated with a reduced risk of cardiovascular disease. Yet, the changes in the serum metabolome after this replacement is not well known. Therefore, the present study aims to identify the metabolites differentiating diets where six energy percentage SFA is replaced with PUFA and to elucidate the association of dietary metabolites with cardiometabolic risk markers.MethodsIn an 8-week, double-blind, randomized, controlled trial, 99 moderately hyper-cholesterolemic adults (25–70 years) were assigned to a control diet (C-diet) or an experimental diet (Ex-diet). Both groups received commercially available food items with different fatty acid compositions. In the Ex-diet group, products were given where SFA was replaced mostly with n-6 PUFA. Fasting serum samples were analysed by untargeted ultra-performance liquid chromatography high-resolution mass spectrometry (UPLC-HRMS). Pre-processed data were analysed by double cross-validated Partial Least-Squares Discriminant Analysis (PLS-DA) to detect features differentiating the two diet groups.ResultsPLS-DA differentiated the metabolic profiles of the Ex-diet and the C-diet groups with an area under the curve of 0.83. The Ex-diet group showed higher levels of unsaturated phosphatidylcholine plasmalogens, an unsaturated acylcarnitine, and a secondary bile acid. The C-diet group was characterized by odd-numbered phospholipids and a saturated acylcarnitine. The Principal Component analysis scores of the serum metabolic profiles characterizing the diets were significantly associated with low-density lipoprotein cholesterol, total cholesterol, and triglyceride levels but not with glycaemia.ConclusionThe serum metabolic profiles confirmed the compliance of the participants based on their diet-specific metabolome after replacing SFA with mostly n-6 PUFA. The participants' metabolic profiles in response to the change in diet were associated with cardiovascular disease risk markers. This study was registered at clinicaltrials.gov as NCT 01679496 on September 6th 2012.

Highlights

  • Cardiovascular disease (CVD) is still one of the leading contributors to death worldwide [1]

  • The intake of energy was similar in the two groups, but the energy percent intake of protein, polyunsaturated fatty acids (PUFA), and fibre was significantly higher in the

  • The untargeted metabolic profiles of serum samples from this 8-week randomized controlled trial with similar foods containing mainly n-6 PUFA vs. saturated fatty acids (SFA) clearly differentiated the subjects from the two groups

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Summary

Introduction

Cardiovascular disease (CVD) is still one of the leading contributors to death worldwide [1]. General dietary recommendations and WHO guidelines suggest that replacing saturated fatty acids (SFA) with polyunsaturated fatty acids (PUFA) reduces the risk of CVD by decreasing LDL-cholesterol levels [3,4,5]. Despite this solid evidence, it has been suggested that foods. The “Healthy Nordic Diet” (HND) is based on the Nordic Nutrition Recommendations [8,9,10] and one of the characteristics of HND compared to the average habitual Nordic diet is the source and type of fat. In an HND, a higher amount of dietary fat derives from plant sources, such as rapeseed oil and sunflower oil rich in n-6 PUFAs instead of dairy products rich in SFAs

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