Modifying Serum Plant Sterol Concentrations: Effects on Markers for Whole Body Cholesterol Metabolism in Children Receiving Parenteral Nutrition and Intravenous Lipids.

BACKGROUND: Non-cholesterol sterols are validated markers for fractional intestinal cholesterol absorption (cholestanol) and endogenous cholesterol synthesis (lathosterol). This study's objective was to evaluate markers for cholesterol synthesis and absorption in children exposed to two different intravenous lipid emulsions that rapidly change serum plant sterol concentrations as part of their parenteral nutrition (PN). METHODS: Serum samples from two different studies were used: (1) nine PN-dependent children with intestinal failure associated liver disease (IFALD) whose soy-based, plant sterol-rich lipid (SO) was replaced with a fish-based, plant sterol-poor (FO) lipid; and (2) five neonates prescribed SO after birth. In the first study, samples were collected at baseline (prior to FO initiation) and after 3 and 6 months of FO. In study 2, samples were collected at 1 and 3 weeks of age. RESULTS: In study 1, a 7-fold reduction in campesterol, a 12-fold reduction in sitosterol, and a 15-fold reduction in stigmasterol was observed 6 months after switching to FO. Serum cholesterol concentrations did not change, but cholesterol-standardized lathosterol increased (3-fold) and cholesterol-standardized cholestanol decreased (2-fold). In study 2, after 3 weeks of SO, sitosterol and campesterol concentrations increased 4-5 fold. At the same time, cholesterol-standardized lathosterol increased 69% and cholesterol-standardized cholestanol decreased by 29%. CONCLUSION: Based on these finding we conclude that changes in serum plant sterol concentrations might have direct effects on endogenous cholesterol synthesis, although this needs to be confirmed in future studies. Moreover, we speculate that this changed synthesis subsequently affects intestinal cholesterol absorption.

The effects of vitamin E or lipoic acid supplementation on oxyphytosterols in subjects with elevated oxidative stress: a randomized trial.

Despite increased serum plant sterol concentrations after consumption of plant sterol enriched margarines, plasma oxyphytosterol concentrations were not increased in healthy subjects. Here, we assessed plasma oxyphytosterol concentrations and whether they are affected by antioxidants in subjects with elevated oxidative stress. Twenty subjects with impaired glucose tolerance (IGT) or type 2 diabetes (DM2) consumed for 4 weeks placebo, vitamin E (804 mg/d) or lipoic acid capsules (600 mg/d). Plasma and blood cell oxyphytosterol and oxycholesterol concentrations were determined in butylated hydroxytoluene-enriched EDTA plasma via GC-MS. Also, markers reflecting oxidative stress and antioxidant capacity were measured. Plasma oxycampesterol and oxysitosterol concentrations were 122% and 83% higher in IGT or DM2 subjects than in healthy subjects, as determined in an earlier study. Vitamin E or lipoic acid supplementation did not reduce plasma oxyphytosterol and oxycholesterol concentrations, or other markers reflecting oxidative stress or antioxidative capacity. Concentrations of different oxyphytosterols correlated within plasma, and within red blood cells and platelets. However, plasma and blood cell oxyphytosterol levels did not correlate. Although plasma oxyphytosterol concentrations are higher in IGT or DM2 subjects than in healthy subjects, 4-weeks vitamin E or lipoic acid supplementation does not lower plasma oxycholesterol or oxyphytosterol concentrations.

Effects of plant sterol- or stanol-enriched margarine on fasting plasma oxyphytosterol concentrations in healthy subjects.

BACKGROUND: Consumption of plant sterols and plant stanols reduces low-density lipoprotein cholesterol (LDL-C) concentrations. At the same time, plasma plant sterol concentrations will increase after plant sterol consumption, but decrease after plant stanol consumption. In contrast to plant stanols, plant sterols can undergo oxidation and form oxyphytosterols. Findings from in vitro and animal studies suggest that oxyphytosterols might be atherogenic. OBJECTIVE: The objective was to examine whether plant sterol and stanol consumption changes fasting plasma oxyphytosterol concentrations. DESIGN: A randomized, double blind, cross-over study was performed in which 43 healthy subjects (18-70 years) consumed for 4 weeks a plant sterol-enriched (3.0 g/d of plant sterols), a plant stanol-enriched (3.0 g/d of plant stanols), and a control margarine separated by wash-out periods of 4 weeks. Oxyphytosterol concentrations were determined in BHT-enriched plasma via GC-MS. RESULTS: Compared to control, serum LDL-C concentrations were reduced after plant sterol (-8.1%; p < 0.001) and plant stanol consumption (-7.8%; p < 0.001). Plant sterol consumption did not change plasma oxyphytosterol concentrations. On the other hand, intake of the plant stanol margarine reduced 7ß-OH-campesterol by 0.07 ng/mL (~14%; p < 0.01) and by 0.07 ng/mL (~15%; p < 0.01) compared with the control and sterol margarines, respectively. When standardized for serum cholesterol, effects on these oxyphytosterols were comparable. In addition, plant stanol intake reduced cholesterol-standardized 7-keto-campesterol levels compared with plant sterol intake (p < 0.05). CONCLUSIONS: Daily consumption of a plant sterol-enriched margarine does not increase oxyphytosterol concentrations, while plant stanol consumption may reduce the concentrations of the oxidative plant sterol metabolites 7ß-OH-campesterol and 7-keto-campesterol.