Mahmoud Raeini-Sarjaz

Deuterium Uptake and Plasma Cholesterol Precursor Levels Correspond as Methods for Measurement of Endogenous Cholesterol Synthesis in Hypercholesterolemic Women

To assess the validity of two techniques used to measure human cholesterol synthesis, the rate of uptake of deuterium (D) into plasma free cholesterol (FC), and plasma cholesterol precursor (squalene, lanosterol, desmosterol and lathosterol) levels were compared in 14 women [65–71 yr with low density lipoprotein-cholesterol (LDL-C)≥3.36 mmol·l−1]. Subjects consumed each of six diets for 5-wk periods according to a randomized crossover design. The experimental diets included a baseline diet (39% energy as fat, 164 mg chol·4.2 MJ−1) and five reduced-fat diets (30% of energy as fat), where two-thirds of the fat was either soybean oil; squeeze, tub or stick margarines; or butter. Fractional and absolute synthesis rates (FSR and ASR) of FC were determined using the deuterium incorporation (DI) method, while cholesterol precursor levels were measured using gas-liquid chromatography. Data were pooled across diets for each variable and correlation coefficients were calculated to determine if associations were present. There was good agreement among levels of the various cholesterol precursors. In addition, FSR in pools/d (p·d−1) and ASR in grams/d (g·d−1) were strongly associated with lathosterol (r=0.72 and 0.71, P=0.0001), desmosterol (r=0.75 and 0.75, P=0.0001), lanosterol (r=0.67 and 0.67), and squalene (r=0.69 and 0.68) when levels of the precursors were expressed as μmol·mmol−1C. Significant but lower correlations were observed between the D uptake and plasma cholesterol precursor levels when the latter were expressed in absolute amounts (μmol·L−1). The wide range of fatty acid profiles of the experimental diets did not influence the degree of association between methods. In conclusion, the DI method and levels of some cholesterol precursors correspond as methods for shortterm measurement of cholesterol synthesis.

Injected phytosterols/stanols suppress plasma cholesterol levels in hamsters

Although plant sterols are known to suppress intestinal cholesterol absorption, whether plasma and hepatic lipid levels are influenced through non-gut related internal mechanisms has not been established. To examine this question 50 male hamsters were divided into 5 groups and fed semi-purified diets containing 20% energy as fat and 0.25% (w/w) cholesterol ad libitum for 60 days. The control group (i) received diet alone, while four additional groups consumed the diet plus one of four equivalent phytosterol mixtures (5 mg/kg/day) given either as (ii) tall oil phytosterols/stanols mixed with diet (oralSA), (iii) tall oil phytosterols/stanols subcutaneously injected (subSA), (iv) soybean oil phytosterols alone mixed with diet (oralSE), or (v) soybean oil subcutaneous injected phytosterols alone (subSE). The control group and both orally supplemented groups also received placebo subcutaneous sham injections. Neither food consumption, body weight, nor liver weight differed across treatment groups. Subcutaneous administration of SA and SE decreased plasma total cholesterol levels by 21% and 23% (p < 0.0001) and non-apolipoprotein-A cholesterol concentrations by 22% and 15% (p < 0.0002), respectively, compared to control. HDL cholesterol and TG concentrations remained unchanged across all groups, except for a decline of 25% (p < 0.0001) in HDL concentration in the subSE group versus control. Plasma campesterol levels were lower (p < 0.05) in the subSA group relative to all other groups. Plasma campesterol:cholesterol and campesterol:sitosterol ratios were, however, higher (p < 0.0001) for both the oral and subSE groups. Hepatic cholesterol levels were higher (p < 0.0001) in the oral and subSE phytosterol groups by 30% and 31%, respectively, relative to control. We conclude that low doses of subcutaneously administered plant sterols reduce circulating cholesterol levels through mechanisms other than inhibiting intestinal cholesterol absorption.

Effects of a diet high in plant sterols, vegetable proteins, and viscous fibers (dietary portfolio) on circulating sterol levels and red cell fragility in hypercholesterolemic subjects

Plant sterols, soy proteins, viscous fibers, and nuts are advised for cholesterol reduction, but their combined effect on plant sterol absorption has never been tested. We assessed their combined action on serum sterols in hyperlipidemic subjects who were following low-saturated fat diets before starting the study and who returned to these diets post-test. The 1-mon test (combination) diet was high in plant sterols (1 g/1,000 kcal), soy protein (23 g/1,000 kcal), viscous fiber (9 g/1,000 kcal), and almonds (14 g/1000 kcal). Fasting blood was obtained for serum lipids and sterols, and erythrocytes were obtained for fragility prior to and at 2-wk intervals during the study. The combination diet raised serum campesterol concentrations by 50% and β-sitosterol by 27%, although these changes were not significant after Bonferroni correction; near-maximal rises were found by the end of the first week, but no change was found in red cell fragility despite a 29% reduction in the LDL cholesterol level. No significant associations were observed between changes in red cell fragility and blood lipids or sterols. We conclude that plant sterols had a minimal impact on serum sterol concentrations or red cell fragility in hyperlipidemic subjects on diets that greatly reduced their serum lipids.

Human cholesterol metabolism is modified independently by restriction of dietary energy versus dietary fat

Results: Body weights (BW) declined (p < 0.001) on LE and LFE diets. Total cholesterol (TC) decreased (p < 0.05) only for LF (7.9%) and LE (10.9%) diets. Diet-induced shifts in LDL-C were not observed, although high density lipoprotein cholesterol values declined (p < 0.05) during LF (13.8%) diet. Only LE (31.7%) and TFE (16.6%) diets reduced (p < 0.05) plasma triglyceride (TG). Cholesterogenesis at 4 wk were lower (p < 0.05) for all diets compared with TFE. When subjects within the LFE group who failed to lose more than 1.8 kg BW over the feeding period were excluded from the analysis, declines in TC (8.2%) (p < 0.05) and TG (23.4%) (p < 0.05) relative to day 0 were observed. Conclusion: These results demonstrate that energy and fat independently reduce TC by lowering cholesterol biosynthesis; however, the most favorable plasma lipid profile with both reduced TC and TG was achieved through energy restriction accompanied by weight loss, regardless of dietary fat level. Supported by Medical Research Council of Canada.