Background Diets high in saturated fatty acids (SFAs) and greater abdominal obesity are both associated with raised low-density lipoprotein cholesterol (LDL-C) concentrations, an independent cardiovascular disease (CVD) risk marker. Although reducing SFA intake is a public health strategy for CVD prevention, the role of body fat distribution on the relationship between SFA and LDL-C is unclear. Therefore, our objective was to investigate whether the association between dietary SFAs and LDL-C concentrations is related to body composition. Methods In the BODYCON (impact of physiological and lifestyle factors on body composition) study, 409 adults [mean age 42 ± 16 years and median BMI of 23.5 (21.5–25.9) kg/m2] underwent a measure of body composition by dual energy x-ray absorptiometry, assessment of habitual dietary intake using a 4-day weighed food diary and physical activity level using a tri-axial accelerometer. Blood pressure was measured, and a fasting blood sample was collected to determine cardiometabolic disease risk markers. Correlations between body composition, circulating risk markers and dietary macronutrients were assessed prior to multivariate regression analysis. The effect of increasing intakes of dietary SFA on outcome measures was assessed using ANCOVA after adjusting for covariates. Results Abdominal visceral adipose tissue (VAT) mass was moderately positively correlated with total cholesterol (TC), LDL-C, systolic blood pressure (SBP), diastolic blood pressure and HOMA-IR (rs = 0.25–0.44, p < 0.01). In multiple regression analysis, 18.3% of the variability in LDL-C was explained by SFA intake [% total energy (TE)], abdominal VAT mass, carbohydrate%TE and fat%TE intakes. When data were stratified according to increasing SFA%TE intakes, fasting TC, LDL-C and non-high-density lipoprotein-cholesterol were higher in Q4 compared with Q2 (p ≤ 0.03). SBP was higher in Q4 versus Q3 (p = 0.01). Android lean mass was also higher in Q3 versus Q1 (p = 0.02). Other anthropometric and CVD risk markers were not different across quartile groups. Conclusions Although dietary SFA was found to explain 9% of the variability in LDL-C, stratification of data according to quartiles of SFA intake did not reveal a dose-dependent relationship with LDL-C concentration. Furthermore, this association appeared to be independent of abdominal obesity in this cohort. Clinical Trail registration: Trial registration: clinicaltrials.gov as NCT02658539. Registered 20 January 2016, https://clinicaltrials.gov/ct2/show/NCT02658539.

A current dietary recommendation to reduce of cardiovascular diseases (CVD) is to decrease intake of dietary saturated fatty acids (SFA) to 10 % total energy. One of the key mechanistic links between SFA and CVD is the impact of SFA in raising serum lowdensity lipoprotein cholesterol (LDL-C). However, this response displays a high degree of inter-individual variation (1). The Reading, Imperial, Surrey Saturated fat Cholesterol Intervention (RISSCI) study has been designed to investigate the metabolic mechanisms underlying this variation in LDL-C response. A dietary exchange model has been developed for the RISSCI study to deliver diets with a high (18 % total energy) and lower (≤ 10 % total energy) content of SFA by its replacement with polyunsaturated (PUFA) and monounsaturated fatty acids (MUFA), to reproduce the variation in LDL-C observed in human intervention studies. This abstract presents interim data as evidence for the efficacy of this dietary exchange model. Data from twenty healthy male participants (51 ± 10 y; 24 ± 3 kg/m 2) recruited at the Universities of Surrey and Reading were included in this interim analysis. A dietary exchange model using exchangeable sources of dietary fat (butter/spreads, oils, dairy foods and snacks)-equating to 40 g/d of fat-was devised for the two 4-week dietary interventions: a high (18 %), followed sequentially by a low (≤10 %) SFA diet. Dietary intakes were assessed at baseline and in the final week of the two dietary intervention periods using 4-day food diaries. Data were analysed using one-way repeated measures ANOVA with the Holm procedure used to correct for multiple pairwise comparisons. Data are presented as mean ± SD. Dietary compositional targets were broadly met (Table), with significantly higher SFA intakes and trends in favour of lower PUFA and MUFA intakes, during the high SFA diet compared to the low SFA diet. There were no other significant differences between the two intervention diets in total energy or other macronutrient intakes. Our initial findings indicate the flexible dietary exchange model was successful in substituting SFA with unsaturated fatty acids in free-living men. This exchange model will be used subsequently in the RISSCI study, to investigate the mechanisms underlying the inter-individual variation in LDL-C response to SFA.

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.

Body mass index (BMI) has been suggested to play an important role in the relationship between the APOLIPOPROTEIN (APO)E genotype and cardiovascular disease (CVD) risk. Using data from the BODYCON cross-sectional study (n = 360 adults) we assessed the association between body composition and CVD risk markers according to APOE genotype, with examination of the role of BMI. In this study cohort, the APOE2/E3 group had lower fasting blood lipids than APOE4 carriers and APOE3/E3 group (p ≤ 0.01). After stratifying the group according to BMI, APOE4 carriers in the normal BMI subgroup had a higher lean mass compared with the APOE3/E3 group (p = 0.02) whereas in the overweight/obese subgroup, the android to gynoid percentage fat ratio was lower in APOE4 carriers than APOE3/E3 group (p = 0.04). Fasting lipid concentrations were only different between the APOE2/E3 and other genotype groups within the normal weight BMI subgroup (p ≤ 0.04). This finding was associated with a lower dietary fibre and a higher trans-fat intake compared with APOE4 carriers, and a lower carbohydrate intake relative to the APOE3/E3 group. Our results confirm previous reports that BMI modulates the effect of APOE on CVD risk markers and suggest novel interactions on body composition, with diet a potential modulator of this relationship.

Purpose UK guidelines recommend dietary saturated fatty acids (SFAs) should not exceed 10% total energy (%TE) for cardiovascular disease prevention, with benefits observed when SFAs are replaced with unsaturated fatty acids (UFAs). This study aimed to assess the efficacy of a dietary exchange model using commercially available foods to replace SFAs with UFAs. Methods Healthy men (n = 109, age 48, SD 11 year) recruited to the Reading, Imperial, Surrey, Saturated fat Cholesterol Intervention-1 (RISSCI-1) study (ClinicalTrials.Gov n°NCT03270527) followed two sequential 4-week isoenergetic moderate-fat (34%TE) diets: high-SFA (18%TE SFAs, 16%TE UFAs) and low-SFA (10%TE SFAs, 24%TE UFAs). Dietary intakes were assessed using 4-day weighed diet diaries. Nutrient intakes were analysed using paired t-tests, fasting plasma phospholipid fatty acid (PL-FA) profiles and dietary patterns were analysed using orthogonal partial least square discriminant analyses. Results Participants exchanged 10.2%TE (SD 4.1) SFAs for 9.7%TE (SD 3.9) UFAs between the high and low-SFA diets, reaching target intakes with minimal effect on other nutrients or energy intakes. Analyses of dietary patterns confirmed successful incorporation of recommended foods from commercially available sources (e.g. dairy products, snacks, oils, and fats), without affecting participants’ overall dietary intakes. Analyses of plasma PL-FAs indicated good compliance to the dietary intervention and foods of varying SFA content. Conclusions RISSCI-1 dietary exchange model successfully replaced dietary SFAs with UFAs in free-living healthy men using commercially available foods, and without altering their dietary patterns. Further intervention studies are required to confirm utility and feasibility of such food-based dietary fat replacement models at a population level.