Determination of variability in serum low density lipoprotein cholesterol response to the replacement of dietary saturated fat with unsaturated fat, in the Reading, Imperial, Surrey Saturated fat Cholesterol Intervention (‘RISSCI’) project

Abstract

Reducing serum low density lipoprotein-cholesterol (LDL-C) by lowering the intake of saturated fatty acids (SFA) to no more than 10% of total energy, remains the mainstay of dietary guidelines to prevent cardiovascular diseases (1). However, there is marked interindividual variation in the serum LDL-C response to the lowering of SFA. If the variability of this response exceeds the potential reduction in LDL-C, then this may limit the usefulness of this recommendation in the UK population. The overall aim of the RISSCI project is to investigate the mechansims underlying variation in serum LDL-C to dietary SFA, to inform more personalised dietary approaches. To achieve this aim, a study (RISSCI-1) was designed to reproduce the variation in serum LDL-C seen in large dietary intervention trials (2,3). Participants showing hyper and hypo-responsiveness to a reduction in SFA could then be selected and retained for further metabolic investigations (RISCCI-2). In RISSCI-1, healthy men were recruited at the Universities of Reading and Surrey (n = 109, mean age 48 (range 30-65 years), mean BMI 25.2 (range 19.1-33.3 kg/m 2), and were asked to follow a high SFA diet (18% total energy) for 4 weeks, and then a diet of lower SFA content, equivalent to that of National dietary guideline (≤ 10% total energy) for a further 4 weeks. Dietary SFA was replaced with mono and polyunsaturated fatty acids (MUFA and PUFA) using a food exchange model (4). The diets were iso-energetic, and dietary intake was determined by 4-day diet diaries (0, 4, 8 weeks). Serum total cholesterol (TC), triacylglycerol (TAG) and HDL-cholesterol (HDL-C) were measured by commercially available colorimetric assays, and LDL-C calculated by the Friedewald formula, at baseline, post-high SFA diet, and post-lower SFA diet. Replacement of dietary SFA with MUFA and PUFA was achieved with good compliance (4) , no effect on BMI, and produced significant reductions in total serum TC and LDL-C of 0.64 (12%) and 0.5 mmol/L (15%), respectively, within 4 weeks (High vs Lower SFA). Inter-individual variation in the change in serum LDL-C ranged from-40% (-1.2mmo/L) to + 20% (3.2mmol/L), and was of a magnitude previously observed in longer-term intervention trials (2,3). These findings support the effectiveness of the dietary guideline to replace SFA with MUFA and PUFA to reduce serum LDL-C, in a short-term intervention. They also demonstrate large inter-individual variation in serum LDL-C, which will allow further investigation of the metabolic and/or genetic origins of this phenomenon in RISCCI-2.

Effects of dietary saturated fatty acids on serum high density lipoprotein, non-high-density lipoprotein and remnant-cholesterol in the Reading Imperial Surrey Saturated fat Cholesterol Intervention (RISSCI-1) study

“…The mean difference for the change in both HDL-C and non-HDL-C increased during the high SFA diet (HDL-C +4.8%, non-HDL-C +5.2%), and decreased during the lower SFA (high UFA) diet (HDL-C -7.4%, non-HDL-C -13.7%). There was no significant difference in the change in serum remnant-cholesterol concentrations between diets.The similar effects of dietary SFA on both serum HDL-C and non-HDL-C in this study, are consistent with a meta-analysis of intervention trials (1), and a previous report of the effects of this dietary exchange on serum LDL-C from the RISSC-1 study (3) , given that LDL-C represents the main component of non-HDL-C. Since dietary-induced changes in HDL-C may not be causally related to protection against ASCVD (4) , the effects of SFA on non-HDL-C are of relatively greater clinical importance.…”

“…The similar effects of dietary SFA on both serum HDL-C and non-HDL-C in this study, are consistent with a meta-analysis of intervention trials (1), and a previous report of the effects of this dietary exchange on serum LDL-C from the RISSC-1 study (3) , given that LDL-C represents the main component of non-HDL-C. Since dietary-induced changes in HDL-C may not be causally related to protection against ASCVD (4) , the effects of SFA on non-HDL-C are of relatively greater clinical importance.…”

Saturated fat and CVD: importance of inter-individual variation in the response of serum low-density lipoprotein cholesterol

“…Inter and intra-individual variation in serum LDL-C has been characterised in response to various dietary exchanges and the NCEP step 2 diets (48,49) . Variation in serum LDL-C in the order of between 0•5-1•5 mmol/l to þ0•5 mmol/l, has also been reported more recently in a number of well-controlled dietary interventions in response to the removal and replacement of SFA with UFA (50,51) (Fig. 1), and addition of SFA as dairy fat (52) .…”

Reproducibility of the Reading Imperial Surrey Saturated fat Cholesterol Intervention (RISSCI-1 and 2) study

“…This study aims to assess the reproducibility of an identical dietary intervention (Reading, Imperial, Surrey Saturated fat Cholesterol Intervention study 1 and 2, RISSCI-1 and RISSCI-2) performed on two occasions, on the outcomes of fasted lipids.In RISSCI-1, healthy male participants (48±11 y; 25±3 kg/m2), recruited at the Universities of Reading and Surrey, were asked to follow a high saturated fatty acid diet (SFA) (18% total energy) followed by a lower SFA diet (10% total energy), each for 4 weeks. The diets were isoenergetic and dietary SFA was replaced with unsaturated fatty acids (UFAs) using a food exchange model (2,3) . The 8-week sequential, non-randomised study, included three visits; visit 1 as a baseline, and visits 2 and 3 after the high and the lower SFA diet, respectively.…”