Abstract
Background: Serum low density lipoprotein (LDL) cholesterol shows marked interindividual variation in response to the replacement of saturated fatty
acids (SFAs) with unsaturated fatty acids (UFAs).
Objectives: To demonstrate the efficacy of United Kingdom guidelines for exchanging dietary SFAs for UFAs, to reduce serum LDL cholesterol and
other cardiovascular disease (CVD) risk factors, and to identify determinants of the variability in LDL cholesterol response.
Methods: Healthy males (n ¼ 109, mean SD age 48 11 y; BMI 25.1 3.3 kg/m2
), consumed a higher-SFA/lower-UFA diet for 4 wk, followed by an
isoenergetic, lower-SFA/higher-UFA diet for 4 wk (achieved intakes SFA:UFA as % total energy 19.1:14.8 and 8.9:24.5, respectively). Serum LDL
cholesterol, CVD risk markers, peripheral blood mononuclear cell (PBMC) gene expression, and dietary intakes were assessed at baseline and the end of
each diet.
Results: Transition from a higher-SFA/lower-UFA to a lower-SFA/higher-UFA diet significantly reduced fasting blood lipids: LDL cholesterol (0.50
mmol/L; 95% confidence interval [CI]: 0.58, 0.42), high-density lipoprotein (HDL) cholesterol (0.11 mmol/L; 95% CI: 0.14, 0.08), and total
cholesterol (TC) (0.65 mmol/L; 95% CI:0.75, 0.55). The dietary exchange also reduced apolipoprotein (apo)B, TC:HDL cholesterol ratio, non-HDL
cholesterol, E-selectin (P < 0.0001), and LDL subfraction composition (cholesterol [LDL-I and LDL-II], apoB100 [LDL-I and LDL-II], and TAG [LDLII]) (P < 0.01). There was also an increase in plasma biomarkers of cholesterol intestinal absorption (β-sitosterol, campesterol, cholestanol), and synthesis
(desmosterol) (P < 0.0001) and fold change in PBMC LDL-receptor mRNA expression relative to the higher-SFA/lower-UFA diet (P ¼ 0.035). Marked
interindividual variation in the change in serum LDL cholesterol response (1.39 to þ0.77 mmol/L) to this dietary exchange was observed, with 33.7%
of this variation explained by serum LDL cholesterol before the lower-SFA/higher-UFA diet and reduction in dietary SFA intake (adjusted R2 27% and
6.7%, respectively). APOE genotype was unrelated to serum LDL cholesterol response to SFA.
Conclusions: These findings support the efficacy of United Kingdom SFA dietary guidelines for the overall lowering of serum LDL cholesterol but
showed marked variation in LDL cholesterol response. Further identification of the determinants of this variation will facilitate targeting and increasing
the efficacy of these guidelines.
The RISSCI-1 study was registered with ClinicalTrials.Gov (No. NCT03270527).