Abstract P287: Hypocholesterolemic Effect of Dietary Stearic Acid May Be Partly Mediated via Alterations in Fecal Bile Acid Metabolism
Authors: Matthan Nirupa R , Rodríguez-Morató Jose , Meng Huicui , Cohen Rebecca , Galluccio Jean , Dolnikowski Gregory , Lichtenstein Alice H 
Published: March 2019

Introduction:
Dietary fat quality has a significant impact on CVD risk. Among the saturated fatty acids (FA), we and others have documented that stearic (18:0) is unique because, unlike shorter chain FA (12:0, 14:0, 16:0), it does not raise plasma LDL-C levels, relative to monounsaturated FA, such as oleic acid (18:1). The mechanism(s) responsible for this effect are not fully elucidated.

Hypothesis:
We tested the hypothesis that the hypocholesterolemic effect of dietary 18:0 and 18:1 relative to 16:0 is mediated by alterations in fecal bile acid metabolism.

Methods:
Primary (cholic, chenodeoxycholic) and secondary bile acids (SBA: lithocholic [LA], deoxycholic [DCA]) were quantified in stool samples from a randomized controlled cross-over trial examining the effect of dietary FA on CVD risk factors. Subjects (N=20 postmenopausal women, 50-85 years, BMI 25-35kg/m
2
, LDL-C >100mg/dL) consumed each diet for 35 days separated by a 2 week washout period. Diets provided 55%E carbohydrate, 15%E protein and 30%E fat with half of the fat provided by 16:0, 18:0 or 18:1, respectively. CVD risk factors (lipids, glucose, insulin, inflammatory markers) were measured using standard methodology. For fecal bile acids analysis, freeze dried samples were spiked with the corresponding deuterated internal standards, followed by an overnight extraction, purification and analysis using reversed-phase liquid chromatography coupled with electrospray ionization quadrupole time of flight mass spectrometry. Quantification was by isotopic dilution. Spearman correlation coefficients were calculated between bile acids and CVD risk factors.

Results:
Fecal total SBA levels were significantly lower after subjects consumed the 18:0 (4.5±3.9 umol/g) compared to the 18:1 (6.8±5.7 umol/g) diet, with intermediate levels after the 16:0 diet (5.2±3.6 umol/g). This was predominantly due to significantly lower LA, and to a lesser extent DCA levels. No detectable differences were observed in primary bile acids levels. Total, LA and DCA levels were positively correlated with insulin (r=0.38 to 0.45; p<0.05), hsCRP (r=0.31 to 0.37, p<0.02), TG (r=0.46 to 0.60; p<0.001), VLDL-C (r=0.47 to 0.63; p<0.001), TC/LDL-C (r=0.42 to 0.63; p<0.001) and LDL-C/HDL-C (0.37 to 0.57; p<0.001) ratios, and negatively with HDL-C (r= -0.51 to -0.44; p<0.001) levels. LA levels were also positively correlated with LDL-C levels (r=0.33; p=0.011).

Conclusion:
These data suggest that the hypocholesterolemic effect of dietary 18:0 was not mediated by increased bile acid excretion as was observed with dietary 18:1. Instead, dietary 18:0 appears to have an inhibitory effect on hydrophobic SBA synthesis in the intestine, which in turn could reduce the efficiency of cholesterol solubilization and thus cholesterol absorption. Further studies on the effects of dietary 18:0 on gut microbiome populations involved in SBA synthesis are warranted.