ARTICLE Effect of diets rich in either saturated fat or n-6 polyunsaturated fatty acids and supplemented with long-chain n-3 polyunsaturated fatty acids on plasma lipoprotein proﬁles CB Dias 1 , N Amigo 2,3,4 , LG Wood 5 , X Correig 2,3 and ML Garg 1 BACKGROUND/OBJECTIVES: Abnormalities in lipoprotein proﬁles (size, distribution and concentration) play an important role in the pathobiology of atherosclerosis and coronary artery disease. Dietary fat, among other factors, has been demonstrated to modulate lipoprotein proﬁles. We aimed to investigate if background dietary fat (saturated, SFA versus omega-6 polyunsaturated fatty acids, n-6PUFA) was a determinant of the effects of LCn-3PUFA supplementation on lipoprotein proﬁles. SUBJECTS/METHODS: A randomized controlled clinical intervention trial in a parallel design was conducted. Healthy subjects (n = 26) were supplemented with 400 mg eicosapentaenoic acid plus 2000 mg docosahexaenoic acid daily and randomized to consume diets rich in either SFA or n-6PUFA for a period of 6 weeks. Blood samples, collected at baseline and after 6 weeks of intervention, were assessed for plasma lipoprotein proﬁles (lipoprotein size, concentration and distribution in subclasses) determined using nuclear magnetic resonance spectroscopy. RESULTS: Study participants receiving the SFA or the n-6PUFA enriched diets consumed similar percentage energy from fat (41 and 42% respectively, P = 0.681). However, subjects on the SFA diet consumed 50% more energy as saturated fat and 77% less as linoleic acid than those consuming the n-6PUFA diet (P o0.001). The diets rich in SFA and n-6PUFA reduced the concentration of total very-low-density lipoprotein (VLDL) particles (P o0.001, both), and their subclasses and increased VLDL (P = 0.042 and P = 0.007, respectively) and LDL (P = 0.030 and 0.027, respectively) particle size. In addition, plasma triglyceride concentration was signiﬁcantly reduced by LCn-3PUFA supplementation irrespective of the dietary fat. CONCLUSIONS: LCn-3PUFA modulated lipoprotein proﬁles in a similar fashion when supplemented in diets rich in either SFA or n-6PUFA. European Journal of Clinical Nutrition advance online publication, 10 May 2017; doi:10.1038/ejcn.2017.56 INTRODUCTION Abnormalities in lipoprotein proﬁles have been associated with coronary heart disease risk in men 1 and women. 2–5 Evidence suggests that coronary heart disease risk is increased by larger very-low-density lipoprotein (VLDL) particle sizes, smaller high- density lipoprotein (HDL) and LDL particle sizes, and increased concentration of small LDL and large VLDL particles; although the ideal lipoprotein proﬁles for the prevention of coronary heart disease may vary according to age, gender and health status. 1,6 A variety of factors can modulate lipoprotein proﬁles, including dietary habits 7 or physical activity. 8 Long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA), despite some controversy, 9 are well known for their health beneﬁts, particularly in the prevention of coronary heart disease, due to their capacity to help manage hyperlipidaemia, 10 inﬂammation 11 and platelet aggregation, 11,12 as well as their potential to modulate lipoprotein proﬁles. Dietary supplementa- tion with LCn-3PUFA has been shown to decrease the concentra- tion of small HDL particles, 13 and increase the concentration of large HDL particles 13–15 and the average HDL particle size, 16 although change in HDL particle size has not been observed in all studies. 15,17 LCn-3PUFA supplementation has also been shown to decrease VLDL particle size 15,18 and large and medium VLDL particle concentration. 14 However, the effect of LCn-3PUFA supplementation on the LDL proﬁle is heterogeneous. Some authors suggest an increase in LDL particle size, 15,19,20 while others have not observed change in LDL size 17,21–23 or have even observed a decrease in particle size. 13 The literature also suggests an increase in the concentration of medium and large LDL particles, and a decrease in small particles, despite no change in the average size of the particles. 14,15,22 In all the above mentioned studies involving LCn-3PUFA supplementation and lipoprotein proﬁles, little attention has been given to the other components of the diet, especially the amount and type of the fats consumed. The human diet comprises a mixture of fats and even after supplementation and increase in seafood consumption, LCn-3PUFA remains a minor proportion of the total fat consumed. We have recently demonstrated that LCn-3PUFA are incorporated in plasma and erythrocytes to a greater extent when consumed with a diet rich in saturated fats compared to a diet rich in n-6PUFA. 24 The aim of this study was to examine whether the background 1 Nutraceuticals Research Group, School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, New South Wales, Australia; 2 Metabolomics Platform, Rovira i Virgili University, IISPV, Tarragona, Spain; 3 Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), C/ Monforte de Lemos 3-5, Madrid, Spain; 4 Biosfer Teslab, Plaça Prim 10, 2on 5a, Reus, Spain and 5 Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, The University of Newcastle, New Lambton, New South Wales, Australia. Correspondence: Professor ML Garg, Nutraceuticals Research Group, School of Biomedical Sciences and Pharmacy, The University of Newcastle, 305C Medical Science Building, Callaghan, New South Wales 2308, Australia. E-mail: manohar.garg@newcastle.edu.au Received 11 December 2016; revised 26 February 2017; accepted 22 March 2017 European Journal of Clinical Nutrition (2017), 1 – 6 © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved 0954-3007/17 www.nature.com/ejcn