Variation of LDL cholesterol in response to the replacement of saturated with unsaturated fatty acids: a nonrandomized, sequential dietary intervention; the Reading, Imperial, Surrey, Saturated fat Cholesterol Intervention ("RISSCI"-1) study.
Study Goal
The researchers aimed to evaluate the efficacy of UK dietary guidelines for replacing saturated fatty acids (SFAs) with unsaturated fatty acids (UFAs) in reducing LDL cholesterol and other CVD risk factors, and to identify determinants of variability in LDL cholesterol response.
Results Summary
Transitioning from a higher-SFA to a lower-SFA diet significantly reduced LDL cholesterol, HDL cholesterol, total cholesterol, and other CVD risk markers, with notable interindividual variability in LDL response. The study also observed changes in cholesterol absorption biomarkers and PBMC LDL-receptor mRNA expression.
Population
Healthy males (n = 109, mean age 48 ± 11 years, BMI 25.1 ± 3.3 kg/m²).
Effective Dosage
SFA:UFA as % total energy—19.1:14.8 (higher-SFA/lower-UFA diet) and 8.9:24.5 (lower-SFA/higher-UFA diet).
Duration
4 weeks per diet phase (8 weeks total).
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
Transition from a higher-SFA/lower-UFA to a lower-SFA/higher-UFA diet | decrease | fasting blood lipids: LDL cholesterol | Healthy males (n = 109, mean ± SD age 48 ± 11 y; BMI 25.1 ± 3.3 kg/m2) | -0.50 mmol/L; 95% confidence interval [CI]: -0.58, -0.42 | significantly reduced | #1 |
Transition from a higher-SFA/lower-UFA to a lower-SFA/higher-UFA diet | decrease | fasting blood lipids: high-density lipoprotein (HDL) cholesterol | Healthy males (n = 109, mean ± SD age 48 ± 11 y; BMI 25.1 ± 3.3 kg/m2) | -0.11 mmol/L; 95% CI: -0.14, -0.08 | significantly reduced | #2 |
Transition from a higher-SFA/lower-UFA to a lower-SFA/higher-UFA diet | decrease | fasting blood lipids: total cholesterol (TC) | Healthy males (n = 109, mean ± SD age 48 ± 11 y; BMI 25.1 ± 3.3 kg/m2) | -0.65 mmol/L; 95% CI:-0.75, -0.55 | significantly reduced | #3 |
The dietary exchange | decrease | apolipoprotein (apo)B | Healthy males (n = 109, mean ± SD age 48 ± 11 y; BMI 25.1 ± 3.3 kg/m2) | P < 0.0001 | reduced | #4 |
The dietary exchange | decrease | TC:HDL cholesterol ratio | Healthy males (n = 109, mean ± SD age 48 ± 11 y; BMI 25.1 ± 3.3 kg/m2) | P < 0.0001 | reduced | #5 |
The dietary exchange | decrease | non-HDL cholesterol | Healthy males (n = 109, mean ± SD age 48 ± 11 y; BMI 25.1 ± 3.3 kg/m2) | P < 0.0001 | reduced | #6 |
The dietary exchange | decrease | E-selectin | Healthy males (n = 109, mean ± SD age 48 ± 11 y; BMI 25.1 ± 3.3 kg/m2) | P < 0.0001 | reduced | #7 |
The dietary exchange | decrease | LDL subfraction composition (cholesterol [LDL-I and LDL-II], apoB100 [LDL-I and LDL-II], and TAG [LDL-II]) | Healthy males (n = 109, mean ± SD age 48 ± 11 y; BMI 25.1 ± 3.3 kg/m2) | P < 0.01 | reduced | #8 |
The dietary exchange | increase | plasma biomarkers of cholesterol intestinal absorption (β-sitosterol, campesterol, cholestanol) | Healthy males (n = 109, mean ± SD age 48 ± 11 y; BMI 25.1 ± 3.3 kg/m2) | P < 0.0001 | increase | #9 |
The dietary exchange | increase | plasma biomarkers of cholesterol synthesis (desmosterol) | Healthy males (n = 109, mean ± SD age 48 ± 11 y; BMI 25.1 ± 3.3 kg/m2) | P < 0.0001 | increase | #10 |
The dietary exchange | increase | PBMC LDL-receptor mRNA expression relative to the higher-SFA/lower-UFA diet | Healthy males (n = 109, mean ± SD age 48 ± 11 y; BMI 25.1 ± 3.3 kg/m2) | P = 0.035 | fold change | #11 |
this dietary exchange | neutral | serum LDL cholesterol response | Healthy males (n = 109, mean ± SD age 48 ± 11 y; BMI 25.1 ± 3.3 kg/m2) | -1.39 to +0.77 mmol/L | marked interindividual variation in the change in | #12 |
- | no change | serum LDL cholesterol response to SFA | - | - | was unrelated to | #13 |
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 = 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 [LDL-II]) (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 = 0.035). Marked interindividual variation in the change in serum LDL cholesterol response (-1.39 to +0.77 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).