title: The effects of dietary saturated fatty acids on blood cholesterol response and body composition
Creators: name: Ozen, Ezgi
Publisher: name: University of Reading
Year: 2022

description: Reducing dietary saturated fat (SFA) intake via replacing it with unsaturated fatty acids (UFA) 
is a public healthy strategy for cardiovascular disease (CVD) prevention. However, with some 
studies reporting inter-individual variability in the low-density lipoprotein cholesterol (LDL-C) response to lowering dietary SFA, there is considerable interest in potential determinants 
underlying the responsiveness of LDL-C to fat intake. Human studies suggest that dietary fat 
composition affects body fat distribution with higher SFA intakes proposed to be associated 
with abdominal fat accumulation and greater CVD risk. However, it is not clear whether the 
variability in LDL-C response to dietary SFA intake is related to changes in body composition.
The relationship between dietary SFA intake with CVD risk markers and body composition 
was investigated using a cross-sectional (BODYCON, Chapter 2) and an 8-week sequential 
dietary intervention (RISSCI, Chapter 3) study. BODYCON included 409 healthy adults aged 
18-70y, with data collected for total body composition, dietary intake, physical activity levels 
and circulating CVD risk markers. Although dietary SFA and abdominal visceral adipose tissue 
explained 9% of the variability in LDL-C, there was a lack of a dose-dependent relationship 
between increasing quartiles of dietary SFA%TE intake and these determinants, with total and 
LDL-C concentrations lower in Q2 (10.1-11.9%TE) than Q4 (14.9-38.7%TE) (p≤0.05). Of the 
anthropometric measures, only lean mass within the trunk (android) region was greater in Q3 
(12.0-14.8%TE) compared to Q1 (1.9-10.0%TE) (p=0.02). Therefore, findings from the 
BODYCON study suggested that the effect of dietary SFA on LDL-C may be independent of 
body fat distribution. In the RISSCI study (n=41/109), significant reductions in fasting lipids 
(total, high density lipoprotein and LDL-C and triacylglycerol) (on average 10-15%, p&lt;0.01) 
and percentage of android body fat were evident after replacing 8% dietary SFA with UFA. 
This suggested that, in the RISSCI study, the beneficial effects of replacing dietary SFA with UFA on lipid CVD risk markers was associated with a reduction in central obesity in healthy 
men. 
To provide insights into the mechanisms underlying the effects of dietary fat on LDL-C, the 
expression of genes involved in cholesterol metabolism were measured in a subset of the 
RISSCI participants (n=58/109). Compared with the high SFA diet, there was an upregulation 
of the LDL-receptor, ABCG1 and NR1H3 mRNA gene expression in peripheral blood 
mononuclear cells (PBMC) after the low SFA diet. To determine whether the variability in the 
LDL-C response to dietary SFA intake (-39% to +19%) was associated with changes in PBMC 
gene expression, the group was then stratified into responder (n=12) and non-responders (n=13)
according to actual change in LDL-C in response to the change in dietary fat composition. 
Interestingly, prior to the start of the intervention, the fasting LDL-C concentration was 19% 
lower in non-responders compared to responders with a significant reduction in fasting lipids 
after replacing dietary SFA with UFA only evident in the responders group (p≤0.05). Although 
there was a non-significant tendency for the LDL-R mRNA expression to be increased in both 
responder and non-responders after replacing dietary SFA with UFA, it was only in non-responders that the ABCG1 and NR1H3 mRNA expressions were significantly upregulated 
after the low SFA diet (p≤0.01) (Chapter 4).
Studies investigating the associations between APOLIPOPROTEIN (APO)E genotype with 
CVD risk markers have generated inconsistent results, with a small number of studies 
suggesting that BMI plays an important role in this relationship. Using data from BODYCON 
(n=360), fasting blood lipids were found to be lower in the APOE2/E3 than the APOE3/E3
group and APOE4 carriers in the normal BMI subgroup only (p≤0.04) (Chapter 5). Lower 
dietary fibre (g) and trans-fat (%TE) intake in the APOE2/E3 participants than APOE4 carriers, 
and a lower carbohydrate (%TE) intake relative to the APOE3/E3 group were also evident in 
the normal BMI subgroup. APOE x BMI interactions on body weight and android fat mass were observed (p≤0.01). While lean mass was higher in APOE4 carriers than APOE3/E3 in the 
normal BMI subgroup (p=0.02), the android:gynoid fat ratio was lower in APOE4 carriers than 
APOE3/E3 in the overweight/obese subgroup (p=0.04). Future studies should confirm the 
APOE-body composition association.
In summary, by using a combination of cross-sectional and interventional study designs, 
this thesis has generated novel findings into the role of dietary SFA on CVD risk markers, body 
fat distribution and responsiveness of genes regulating cholesterol metabolism to dietary fat 
manipulation. More studies are needed to determine mechanisms underlying the inter-individual variability in LDL-C response to dietary fat manipulation and to confirm APOE body composition association to provide more effective personalised dietary advice.