Animal and in vitro studies suggest that olive oil phenols are effective antioxidants. The most abundant phenols in olive oil are the nonpolar oleuropein-and ligstroside-aglycones and the polar hydroxytyrosol and tyrosol. The aim of this study was to gain more insight into the metabolism of those phenols in humans. We measured their absorption in eight healthy ileostomy subjects. We also measured urinary excretion in the ileostomy subjects and in 12 volunteers with a colon. Subjects consumed three different supplements containing 100 mg of olive oil phenols on separate days in random order. Ileostomy subjects consumed a supplement with mainly nonpolar phenols, one with mainly polar phenols and one with the parent compound oleuropein-glycoside. Subjects with a colon consumed a supplement without phenols (placebo) instead of the supplement with oleuropein-glycoside. Ileostomy effluent and urine were collected for 24 h after supplement intake. Tyrosol and hydroxytyrosol concentrations were low (Ͻ 4 mol/100 mol of intake) in the ileostomy effluent, and no aglycones were detected. We estimated that the apparent absorption of phenols was at least 55-66% of the ingested dose. Absorption was confirmed by the excretion of tyrosol and hydroxytyrosol in urine. In ileostomy subjects, 12 mol/100 mol and in subjects with a colon, 6 mol/100 mol of the phenols from the nonpolar supplement were recovered in urine as tyrosol or hydroxytyrosol. In both subject groups, 5-6 mol/100 mol of the phenols was recovered from the polar supplement. When ileostomy subjects were given oleuropein-glycoside, 16 mol/100 mol was recovered in 24-h urine, mainly in the form of hydroxytyrosol. Thus, humans absorb a large part of ingested olive oil phenols and absorbed olive oil phenols are extensively modified in the body. J. Nutr. 132: 409 -417, 2002.

Objective: We reviewed the bioavailability and antioxidant effects of phenols from extra virgin olive oil. Search strategy: We searched the MEDLINE database for the years . To review the bioavailability of olive oil phenols, we selected animal and human studies that studied the absorption, metabolism, and urinary excretion of olive oil phenols. We also estimated the intake of the various phenols in the Mediterranean area. To review the antioxidant effects of olive oil phenols, we included human and animal studies on the effect of olive oil phenols on markers of oxidative processes in the body. We excluded studies without a proper control treatment and studies in which the antioxidant effects of phenols could not be disentangled from those of the fatty acid composition of olive oil. Results: Bioavailability studies in humans show that the absorption of olive oil phenols is probably larger than 55-66 mol%, and that at least 5% is excreted in urine as tyrosol and hydroxytyrosol. Animal studies suggest that phenol-rich olive oil lowers oxidisability of ex vivo low-density lipoprotein (LDL) particles or lowers markers in urine of oxidative processes in the body. In five out of seven human studies, however, these effects of phenols were not found. There are no data on the phenol concentrations in plasma that are attainable by intake of olive oil. We estimated that 50 g of olive oil per day provides about 2 mg or B13 mmol of hydroxytyrosol-equivalents per day, and that the plasma concentration of olive oil phenols with antioxidant potential resulting from such an intake can be at most 0.06 mmol/l. This is much lower than the minimum concentrations of these phenols (50-100 mmol) required to show antioxidant activity in vitro. Conclusion: Although phenols from olive oil seem to be well absorbed, the content of olive oil phenols with antioxidant potential in the Mediterranean diet is probably too low to produce a measurable effect on LDL oxidisability or other oxidation markers in humans. The available evidence does not suggest that consumption of phenols in the amounts provided by dietary olive oil will protect LDL against oxidative modification to any important extent.

Objective-Functional and morphological changes of the arterial wall already present in young children with heterozygous familial hypercholesterolemia (HeFH) suggest that treatment should be initiated early in life to prevent premature atherosclerotic cardiovascular disease. The purpose of this study was to assess the efficacy and particularly safety of statin therapy in children with HeFH. Methods and Results-We performed a meta-analysis of randomized, double-blind, placebo-controlled trials evaluating statin therapy in children aged 8 to 18 years with HeFH. Six studies (nϭ798 children) with 12 to 104 weeks of treatment were included. Total cholesterol, LDL cholesterol, and apolipoprotein B were significantly reduced, whereas HDL cholesterol and apolipoprotein A1 were significantly increased by statin therapy. No statistically significant differences were found between statin-and placebo-treated children with respect to the occurrence of adverse events (RR 0.

Background-We previously demonstrated in a randomized placebo-controlled trial that 2-year pravastatin treatment induced a significant regression of carotid intima-media thickness (IMT) in 8-to 18-year-old children with familial hypercholesterolemia. Subsequently, we continued to follow up these children to explore the relation between the age of statin initiation and carotid IMT after follow-up on statin treatment. We also examined safety aspects of statin therapy during this long-term follow-up. Methods and Results-All 214 children who initially participated in the previous placebo-controlled study were eligible for the follow-up study. After completion of the placebo-controlled study, all children continued treatment with pravastatin 20 or 40 mg, depending on their age. Blood samples were taken on a regular basis for lipids and safety parameters, and a carotid IMT measurement was performed after an average treatment period of 4.5 years. Follow-up data for 186 children were available for the statistical analyses. Multivariate analyses revealed that age at statin initiation was an independent predictor for carotid IMT after follow-up with adjustment for carotid IMT at initiation of statin treatment, sex, and duration of treatment. Early initiation of statin treatment was associated with a subsequently smaller IMT. Furthermore, no serious laboratory adverse events were reported during follow-up, and statin treatment had no untoward effects on sexual maturation. Conclusions-These data indicate that early initiation of statin treatment delays the progression of carotid IMT in adolescents and young adults. The present study shows for the first time that early initiation of statin therapy in children with familial hypercholesterolemia might be beneficial in the prevention of atherosclerosis in adolescence. (Circulation.

BackgroundThe risk of premature cardiovascular disease in patients with familial hypercholesterolemia (FH) can be profoundly reduced by cholesterol-lowering therapy, and current guidelines for FH advocate ambitious low-density lipoprotein cholesterol (LDL-C) goals. In the present study, we determined whether these goals are reflected in current clinical practice once FH has been diagnosed.Methodology/Principal FindingsIn 2008, we sent questionnaires to all subjects (aged 18–65 years) who were molecularly diagnosed with FH in the year 2006 through the screening program in the Netherlands. Of these 1062 subjects, 781 completed the questionnaire (46% males; mean age: 42±12 years; mean LDL-C at molecular diagnosis (baseline): 4.1±1.3 mmol/L). The number of persons that used cholesterol-lowering therapy increased from 397 (51%) at baseline to 636 (81%) after diagnosis. Mean treated LDL-C levels decreased significantly to 3.2±1.1 mmol/L two years after diagnosis. Only 22% achieved the LDL-C target level of ≤2.5 mmol/L.Conclusions/SignificanceThe proportion of patients using cholesterol-lowering medication was significantly increased after FH diagnosis through genetic cascade screening. The attained LDL-C levels were lower than those reported in previous surveys on medication use in FH, which could reflect the effect of more stringent lipid target levels. However, only a minority of the medication users reached the LDL-C target.

Some studies have suggested that a modest increase of plant sterol levels is a risk factor for coronary artery disease (CAD). We studied the relationship between plant sterol levels and CAD risk in a prospective nested casecontrol study consisting of 373 cases and 758 controls. Sitosterol and campesterol concentrations did not differ between cases and controls [sitosterol, 0.21 vs. 0.21 mg/dl (P 5 0.1); campesterol, 0.31 vs. 0.32 mg/dl (P 5 0.5)]. The sitosterol-to-cholesterol ratio was significantly lower in cases than in controls (1.19 vs. 1.29 mg/mg; P 5 0.008), whereas the campesterol-to-cholesterol ratio did not differ significantly (1.78 vs. 1.88 mg/mg; P 5 0.1). Plant sterol concentrations correlated positively with cholesterol levels and inversely with body mass index and triglyceride and lathosterol concentrations. Among individuals in the highest tertile of the sitosterol concentration, the unadjusted odds ratio (OR) for future CAD was 0.75 [95% confidence interval (CI) 5 0.56-1.01]. After adjustment for traditional risk factors, the OR was 0.79 (95% CI 5 0.56-1.13). For the campesterol concentration, the unadjusted OR was 0.95 (95% CI 5 0.71-1.29) and the adjusted OR was 0.97 (95% CI 5 0.68-1.39). In this large prospective study, higher levels of plant sterols, at least in the physiological range, do not appear to be adversely related to CAD in apparently healthy individuals.-Pinedo, S., M. N. Vissers, K.

Objective: To study the effects of prolonged intake of cafetiere coffee, which is rich in the diterpenes cafestol and kahweol, on serum aminotransferase and lipid concentrations. Design: Randomised parallel controlled trial. Subjects: 46 healthy men and women aged 19 to 69. Intervention: Consumption of five to six strong cups (0.9 litres) a day of either cafetiere (22 subjects) or filtered coffee (24 subjects) for 24 weeks. Main outcome measures: Mean changes in serum aminotransferase and lipid concentrations. Results: Cafetiere coffee raised alanine aminotransferase concentration by up to 80% above baseline values relative to filtered coffee. After 24 weeks the rise was still 45% (9 U/l (95% confidence interval 3 to 15 U/l), P = 0.007). Alanine aminotransferase concentration exceeded the upper limit of normal in eight of the 22 subjects drinking cafetiere coffee, being twice the upper limit of normal in three of them. Cafetiere coffee raised low density lipoprotein cholesterol concentrations by 9–14%. After 24 weeks the rise was 0.26 mmol/l (0.04 to 0.47 mmol/l) (P = 0.03) relative to filtered coffee. Triglyceride concentrations initially rose by 26% with cafetiere coffee but returned close to baseline values within six months. All increases were reversible after the intervention was stopped. Conclusions: Daily consumption of five to six cups of strong cafetiere coffee affects the integrity of liver cells as suggested by small increases in serum alanine aminotransferase concentration. The effect does not subside with prolonged intake. High intakes of coffee brews rich in cafestol and kahweol may thus be responsible for unexplained increases in this enzyme activity in apparently healthy subjects. Cafetiere coffee also raises low density lipoprotein cholesterol concentration and thus the risk of coronary heart disease. Key messages This randomised study found that cafetiere coffee also increased alanine aminotransferase and low density lipoprotein cholesterol concentrations, and they were still raised after six months of daily intake. Filtered coffee had no effect The increase in liver enzyme activity could be innocuous, but the increase in cholesterol concentration may increase coronary risk and could be a reason to advise patients to drink filtered coffee

No abstract