Date Published: February 6, 2017
Publisher: Public Library of Science
Author(s): Sally Chiu, Paul T. Williams, Ronald M. Krauss, Alberico Catapano.
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.
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).
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.
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. 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). Clinicaltrials.gov NCT00895141.
Current dietary guidelines aim at limiting saturated fat intake in large part because of its ability to increase LDL-cholesterol (LDL-C) levels and presumably, cardiovascular disease (CVD) risk. However, several recent meta-analyses and systematic reviews have concluded that saturated fat per se is not associated with greater CVD risk [1–3]. This may be due in part to differential effects of saturated fat on LDL subclass concentrations. Small and medium sized LDL particles have been shown to be more strongly associated with CVD outcomes than larger LDL [4–7]. We have previously reported results from a dietary intervention trial indicating that increased intake of total saturated fatty acids, particularly myristic (14:0) and palmitic (16:0) acids, correlated with increased plasma levels of larger LDL particles, but not with change in smaller LDL or apoB concentrations . Moreover, in a subsequent clinical trial, we showed that in the context of reduced carbohydrate intake, the increase in LDL-C resulting from exchange of dietary saturated fat for monounsaturated fat was due primarily to higher concentrations of cholesterol-enriched larger LDL, without changes in smaller LDL or apoB . Saturated fat also raises HDL-cholesterol (HDL-C) , which could potentially offset an atherogenic effect of raising LDL-C.
The trial protocol (S1 Protocol) and CONSORT (S1 CONSORT Checklist) checklist are available as supporting information.
Recent evidence has shown that although increased intake of saturated fatty acids can raise LDL-C when substituted for either carbohydrate or cis-unsaturated fatty acids , the substitution for carbohydrate is not associated with higher CVD risk [22–25]. We hypothesized that the dissociation of LDL-C change from effects on CVD risk may be due in part to a preferential effect of saturated fat on cholesterol-enriched large LDL particles, which are not as strongly associated with CVD risk as are small and medium sized LDL particles [4–6]. In contrast, we and others have shown that higher carbohydrate intake promotes selective increases in levels of small LDL particles [9, 26–28]. In one of these studies, we found that in the context of reduced carbohydrate intake (26% E), increased intake of saturated fatty acids derived primarily from dairy fat preferentially raised large LDL without increasing small LDL or apoB concentrations . This is consistent with results from other intervention studies [8, 29–33] and observational cohort studies [34–36] showing that diets high in saturated fat, derived in many cases from dairy sources, increased peak LDL particle diameter, and/or levels of larger LDL without raising levels of smaller LDL particles. Other studies however, have reported no significant effect of saturated fat on LDL particle size distribution [37–40]. In the present study, we found that with substitution of saturated fatty acids derived primarily from dairy foods for monounsaturated fatty acids, increased LDL-C was associated with increased apoB, and total, small, and medium-sized LDL particle concentrations. There were, however, no significant changes in large LDL, large HDL, or LDL peak diameter. We suggest a number of possible factors that may contribute, singly or in combination, to the discrepancy of these findings from those that we reported previously .