Effects of a very high saturated fat diet on LDL particles in adults with atherogenic dyslipidemia: A randomized controlled trial

<div><p>Background</p><p>Previous studies have shown that increases in LDL-cholesterol resulting from substitution of dietary saturated fat for carbohydrate or unsaturated fat are due primarily to increases in large cholesterol-enriched LDL, with minimal changes in small, dense LDL particles and apolipoprotein B. However, individuals can differ by their LDL particle distribution, and it is possible that this may influence LDL subclass response.</p><p>Objective</p><p>The objective of this study was to test whether the reported effects of saturated fat apply to individuals with atherogenic dyslipidemia as characterized by a preponderance of small LDL particles (LDL phenotype B).</p><p>Methods</p><p>Fifty-three phenotype B men and postmenopausal women consumed a baseline diet (55%E carbohydrate, 15%E protein, 30%E fat, 8%E saturated fat) for 3 weeks, after which they were randomized to either a moderate carbohydrate, very high saturated fat diet (HSF; 39%E carbohydrate, 25%E protein, 36%E fat, 18%E saturated fat) or low saturated fat diet (LSF; 37%E carbohydrate, 25%E protein, 37%E fat, 9%E saturated fat) for 3 weeks.</p><p>Results</p><p>Compared to the LSF diet, consumption of the HSF diet resulted in significantly greater increases from baseline (% change; 95% CI) in plasma concentrations of apolipoprotein B (HSF vs. LSF: 9.5; 3.6 to 15.7 vs. -6.8; -11.7 to -1.76; p = 0.0003) and medium (8.8; -1.3 to 20.0 vs. -7.3; -15.7 to 2.0; p = 0.03), small (6.1; -10.3 to 25.6 vs. -20.8; -32.8 to -6.7; p = 0.02), and total LDL (3.6; -3.2 to 11.0 vs. -7.9; -13.9 to -1.5; p = 0.03) particles, with no differences in change of large and very small LDL concentrations. As expected, total-cholesterol (11.0; 6.5 to 15.7 vs. -5.7; -9.4 to -1.8; p<0.0001) and LDL-cholesterol (16.7; 7.9 to 26.2 vs. -8.7; -15.4 to -1.4; p = 0.0001) also increased with increased saturated fat intake.</p><p>Conclusions</p><p>Because medium and small LDL particles are more highly associated with cardiovascular disease than are larger LDL, the present results suggest that very high saturated fat intake may increase cardiovascular disease risk in phenotype B individuals. This trial was registered at clinicaltrials.gov (NCT00895141).</p><p>Trial registration</p><p>Clinicaltrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT00895141" target="_blank">NCT00895141</a>.</p></div

Percent changes from baseline in plasma lipoprotein subfractions and lipoprotein remodeling enzyme activities in men and women with atherogenic dyslipidemia after 3 wk of consuming either a low or high saturated fat diet^a.

<p>Percent changes from baseline in plasma lipoprotein subfractions and lipoprotein remodeling enzyme activities in men and women with atherogenic dyslipidemia after 3 wk of consuming either a low or high saturated fat diet<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0170664#t004fn001" target="_blank">^a</a>.</p

Participant characteristics at randomization (at the end of the baseline diet)^a.

<p>Participant characteristics at randomization (at the end of the baseline diet)<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0170664#t002fn001" target="_blank">^a</a>.</p

CONSORT flow diagram.

<p>CONSORT flow diagram.</p

Composition of baseline and experimental diets^a.

<p>Composition of baseline and experimental diets<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0170664#t001fn001" target="_blank">^a</a>.</p

Percent changes from baseline in plasma lipid and lipoprotein concentrations in men and women with atherogenic dyslipidemia after 3 wk of consuming either a low or high saturated fat diet^a.

<p>Percent changes from baseline in plasma lipid and lipoprotein concentrations in men and women with atherogenic dyslipidemia after 3 wk of consuming either a low or high saturated fat diet<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0170664#t003fn001" target="_blank">^a</a>.</p

Odds ratio (95% confidence interval) for primary disease endpoints (coronary-related deaths, myocardial infarctions, stroke, revascularization for worsening ischemia) per a one standard deviation increment in on-study LDL-peak diameter and LDL-subclass concentrations.

<p>Logistic regression analyses adjusted for baseline age, sex, BMI, current smoking status. Effects are per standard deviation increase in the on-study LDL-peak diameter (8.050 nm), LDL-I (0.185 mmol/L), LDL-IIa (0.234 mmol/L), LDL-IIb (0.326 mmol/L), LDL-IIIa (0.328 mmol/L), LDL-IIIb (0.113 mmol/L), LDL-IVa (0.049 mmol/L), and LDL-IVb (0.039 mmol/L).</p

Regression slope (95% confidence interval) for three-year changes in percent stenosis per nm increase in on-study LDL-peak diameter and per mmol/L increase LDL-cholesterol subfraction concentrations.

<p>Regression slope (95% confidence interval) for three-year changes in percent stenosis per nm increase in on-study LDL-peak diameter and per mmol/L increase LDL-cholesterol subfraction concentrations.</p

Baseline characteristics of study participants.

<p>Age and BMI are displayed as mean±SD, lipoproteins as means±SE</p

Three-year change in percent stenosis by quartiles of LDL-IIIb cholesterol.

<p>Adjusted for age, sex, BMI and smoking, and additional variables as indicated. Adjustment for lipids includes on-study HDL- and LDL-cholesterol and triglyceride concentrations. ^* designates significance relative to the first quartile at P<0.05.</p