Foods containing plant sterol or stanol esters can be beneficial in lowering LDL-cholesterol concentration, a major risk factor for CVD. The present study examined whether high dietary intake of rapeseed oil (RSO) derived plant sterol and stanol esters is associated with increased levels of these components in brain tissue of homozygous and heterozygous Watanabe rabbits, an animal model for familial hypercholesterolemia. Homozygous animals received either a standard diet, RSO stanol or RSO sterol ester while heterozygous animals were additionally fed with 2 g cholesterol/kg to the respective diet form for 120 d (n 9 for each group). Concentrations of cholesterol, its precursor lathosterol, plant sterols and stanols in brain and additionally in liver and plasma were determined by highly sensitive GC -MS. High-dose intake of RSO derived plant sterols and stanols resulted in increased levels of these components in plasma and liver. In brain a limited uptake of plant sterols and stanols was proven, indicating that these compounds passed the blood-brain barrier and may be retained in the brain tissue of Watanabe rabbits. Plant stanol ester feeding lowered plant sterol levels in brain, liver, and plasma. Cholesterol synthesis in brain, indicated by lathosterol, a local surrogate cholesterol synthesis marker, does not seem to be affected by plant sterol or stanol ester feeding. We conclude that high dose intake of plant sterol and stanol esters in Watanabe rabbits results in elevated concentrations of these components not only in the periphery but also in the central nervous system. Phytosterols: Brain cholesterol: LDL receptor: Hypercholesterolemia: AtherosclerosisFortification of margarine and dairy products with plant sterol or plant stanol esters is a current dietary approach to lower elevated plasma cholesterol levels 1 -3 . High levels of total and LDL cholesterol are risk factors for atherosclerosis and CHD, the major cause of morbidity and mortality in the Western world 4 . Watanabe heritable hyperlipidemic (Watanabe) rabbits, the animal model used in the present study, have a defect of the LDL receptor and consequently develop hypercholesterolemia, resulting in atherosclerotic lesions very similar to those in human subjects and xantomas 5 -7 . Comparable to human subjects the heterozygous form of hypercholesterolemia in Watanabe rabbits leads to a 2-3-fold increase in plasma cholesterol, while the homozygous form presents up to 10-fold higher circulating plasma cholesterol levels 6 . The present study was part of the European Union project NOFORISK ('Quantitative risk assessment strategies for novel food') 8 . In this project, a scientific methodology necessary for quantitative risk assessment of 'second generation' novel foods to be marketed in the European Union was developed and validated. The primary goal of the Watanabe rabbit experiments within the project was to evaluate the presumable athero-protective or atherogenic character of plant sterol or stanol ester supplementation in cholesterol-fed heteroz...
BackgroundThe short-term cholesterol-lowering efficacy of plant stanol esters has been open to debate, and the data from different clinical studies with hypercholesterolemic subjects are variable, partly due to lack of systematic studies. Therefore, we investigated the time in days needed to obtain the full cholesterol-lowering effect of stanol esters in hypercholesterolemic subjects.MethodsEleven mildly to moderately hypercholesterolemic subjects consumed stanol ester margarine (2.0 g/day of stanols) as a part of their habitual diet for 14 days and the changes in serum lipid values were measured three times at 4, 8 and 15 days after the initiation of test margarine consumption (0 day). The returning of serum lipid concentrations to baseline was measured two times after 2 or 3 days and after 7 days of the end of the test margarine consumption.ResultsSerum LDL cholesterol concentrations were reduced from 0 day (4.51 ± 0.66 mmol/l) by 3.5% (P = ns), 9.9% (p < 0.05) and 10.2% (P < 0.05) at 4, 8 and 15 days, respectively. Serum campesterol/total cholesterol ratio, an indirect marker of intestinal cholesterol absorption, was significantly reduced on day 4 already. After ending the stanol ester use serum cholesterol concentrations began to return rapidly and after 7 days serum LDL cholesterol was 5.3% less than the initial value (P = ns).ConclusionThe specific effect of plant stanol esters on serum LDL cholesterol can fully be obtained within 1–2 weeks of the use of plant stanol ester-enriched margarine.
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