Campesterol Levels Research Articles

DHA‐enriched high oleic canola oil diet may accelerate the cholesterol synthesis in humans.

Circulating plant sterols are commonly used as surrogate biomarkers of cholesterol absorption, while desmosterol and lathosterol levels indicate cholesterol synthesis. To investigate the health benefits of various dietary oils varying n‐9/n‐6 fatty acid profiles on cholesterol trafficking using markers of cholesterol absorption and synthesis, a double‐blinded randomized crossover clinical trial consisting of five 30‐d periods was conducted. Diets included 60 g/d of canola oil (Canola, 59% OA, 20% LA, 10% ALA), high oleic canola oil (CanoalOleic, 72% OA, 15% LA), high oleic canola/DHA oil (CanolaDHA, 63% OA, 13% LA, 6% DHA), corn/safflower oil (CornSaff, 18% OA, 69% LA) and flax/safflower oil (FlaxSaff, 18% OA, 38% LA, 32% ALA). Total cholesterol and other sterol measures were determined using GC‐FID at endpoints. Results (n=54) showed that CanolaDHA feeding produced the highest serum total cholesterol levels (p<0.05) compared to other four treatments. No differences were observed in desmosterol levels across all diets. CanolaDHA also produced the highest lathosterol (p<0.0001) among all treatments with 27% more than the n‐6 control CornSaff. The sum of sitosterol and campesterol levels within three n‐9 rich diets, Canola, CanolaDHA, and CanolaOleic were higher (p<0.001) than two n‐6 rich diets by 27%, 34% and 20%, respectively. The data suggest that dietary DHA oil may accelerate cholesterol synthesis, resulting in high circulating cholesterol levels while n‐9 rich diets can elevate cholesterol absorption compared to n‐6 rich diets.

Markers of cholesterol metabolism as biomarkers in predicting diabetes in the Finnish Diabetes Prevention Study

Background and aimsWe examined the effect of serum markers of cholesterol synthesis and absorption on the incidence of type 2 diabetes (T2D) in the randomized Finnish Diabetes Prevention Study (DPS). We also explored a possible interaction of ABCG8 rs4299376 on sterol levels and lifestyle intervention. Methods and resultsWe conducted a prospective cohort study including overweight, middle-aged people with impaired glucose tolerance at baseline who participated in the randomized DPS. The primary outcome of the DPS was the diagnosis of T2D based on repeated oral glucose tolerance tests (OGTTs). After active intervention (median of four years, 1994–2001), non-T2D participants were further followed until T2D diagnosis, dropout or the end of 2009. Of these, 340 participants who had β-sitosterol, campesterol, lathosterol and desmosterol measured by gas chromatography-mass spectrometry during the active four-year follow-up and who were not using cholesterol lowering medications were analysed. Surrogate indexes of insulin sensitivity (IS) and secretion were calculated from an OGTT. In adjusted models, plant sterols during the four-year follow-up were associated with lower T2D incidence during the extended eight-year follow-up (HR for 1-SD change in β-sitosterol and campesterol: 0.76 [0.63–0.92], and 0.81 [0.67–0.99], respectively). Lathosterol levels were associated with higher T2D incidence (HR: 1.35 [1.13–1.62]). These associations, though, were not independent of IS. There was an interaction between rs4299376 and study group on β-sitosterol (p = 0.001) and campesterol (p = 0.004) levels during the follow-up. ConclusionsMarkers of low absorption and high synthesis of cholesterol were associated with the risk of developing T2D, mostly ascribed to IS.

Abstract 18611: Increased Absorption and Decreased Synthesis of Cholesterol in Cardiac Sarcoidosis

Introduction: Sarcoidosis is a multisystem inflammatory disease characterised by the formation of granulomas in many tissues. Some reports suggest that the disease is associated with altered lipoprotein cholesterol profiles, but there is no deeper knowledge of cholesterol metabolism in these patients. Hypothesis: We tested the hypothesis that cholesterol metabolism is abnormal in cardiac sarcoidosis (CS). Methods: The study population consisted of 39 patients with histologically verified CS (31 women and 8 men, mean age 53 years) and 124 healthy controls of similar age and gender. 31 of the CS patients were on immunosuppressive treatment. Serum lipids were determined and cholesterol metabolism was evaluated by measuring serum markers of cholesterol absorption (cholestanol, campesterol and sitosterol) and synthesis (desmosterol and lathosterol) as ratios to cholesterol with gas-liquid chromatography. Results: CS was inactive in all patients based on clinical evaluation, cardiac ultrasound, and stable levels of serum TnT and proBNP. Serum total, LDL and HDL cholesterol concentrations (mean±SE) were 5.6±0.2, 3.3±0.1 and 1.5±0.1 mmol/l, respectively, and serum triglyceride averaged 1.7±0.7 mmol/l. These values did not differ from those of controls. Cholesterol absorption markers were higher in CS patients than in controls (eg. serum campesterol level 245±17 vs 190±17 10 2 μmol/mmol of cholesterol, p<0.05). Cholesterol synthesis markers were lower in CS patients than in controls (eg. serum lathosterol level102±8 vs 195±17 10 2 μmol/mmol of cholesterol, p<0.001). Concentrations of serum lipids and non-cholesterol sterols did not associate with the use of immunosuppressive drugs. Markers of cholesterol absorption and synthesis did not correlate with serum TnT levels, but there was a significant positive correlation between proBNP and cholesterol absorption markers (r=0.351, p<0.05). Conclusions: We conclude that, in CS, cholesterol absorption is increased and its synthesis is decreased. The underlying mechanisms remain obscure and deserve further study. This is the first time that abnormal cholesterol metabolism has been described in CS.

Investigation of antihyperglycaemic activity of banana (Musa sp. var. Nanjangud rasa bale) pseudostem in normal and diabetic rats.

Postprandial hyperglycaemia in diabetes could be ameliorated by inhibiting intestinal α-glucosidases, responsible for starch hydrolysis and its absorption. Different parts of banana have been in use in conventional medicinal formulations since ancient times. Its role as an antihyperglycaemic agent has also been studied. This study was aimed at explaining the mechanism of hypoglycaemic effect by ethanol extract of banana pseudostem (EE). Additionally, studies on the active components involved in the effect have also been attempted. EE significantly inhibited mammalian intestinal α-glucosidases and yeast α-glucosidase (IC50 , 8.11 ± 0.10 µg mL(-1) ). The kinetic studies showed that EE inhibited sucrase, maltase and and p-nitrophenyl-α-d-glucopyranoside hydrolysis by mixed-type inhibition. Further, in vivo studies identified that the oral administration (100-200 mg kg(-1) body weight) of EE significantly suppressed the maltose/glucose-induced postprandial plasma glucose elevation and wielded an antihyperglycaemic effect in normal and alloxan-induced diabetic rats. GC-MS analysis of EE revealed high levels of β-sitosterol (29.62%), stigmasterol (21.91%), campesterol (10.85%) and other compounds. These findings suggest that EE might exert an anti-diabetic effect by inhibition of α-glucosidases from the intestine, in turn suppressing the carbohydrate absorption into the bloodstream. Hence the results extend a foundation to the future prospects of the food-derived enzyme inhibitors in treatment of diabetes.

Premature atherosclerosis is not systematic in phytosterolemic patients: Severe hypercholesterolemia as a confounding factor in five subjects

ObjectivePhytosterolemia is a rare autosomal recessive disorder characterized by dramatically elevated circulating levels of plant sterols (PS). Phytosterolemia is believed to be responsible for severe premature atherosclerosis. The clinical, biological and molecular genetic features of 5 patients with phytosterolemia and transient severe hypercholesterolemia challenge this hypothesis. MethodsOur patients were referred for suspected homozygous familial hypercholesterolemia. Despite the phenotype, this diagnosis was invalidated and phytosterolemia was confirmed by the identification of mutations in the ABCG5/ABCG8 transporter complex. Plasma PS were analyzed with a mass spectrometric-gas chromatographic procedure. Vascular status was assessed with carotid ultrasonography and completed (for 4 of the 5 patients) with femoral ultrasonography; additional examinations of cardiovascular status included a stress test, determination of coronary calcium score, echocardiography, non-invasive assessment of endothelium-dependent dilatation and coronarography. ResultsThe 5 patients displayed markedly elevated levels of both β-sitosterol and campesterol (15–30 fold higher than normal values). However, none displayed significant signs of infraclinical premature atherosclerosis (respectively at the ages of 32, 27, 29, 11 and 11 years). All patients were characterized by very high levels of total (>450 mg/dl) and LDL-cholesterol (>350 mg/dl) at diagnosis which decreased markedly on dietary intervention alone. Treatment with cholestyramine or Ezetimibe ± atorvastatin normalized cholesterol levels, although plasma PS concentrations remained elevated. ConclusionThe clinical and biological characteristics of our patients, considered together with reports of cases which equally lack CVD, support the contention that the premature atherosclerosis associated with phytosterolemia in some patients may be due at least in part to mechanisms independent of elevated circulating phytosterol levels.

Kidney Function, Cholesterol Absorption and Remnant Lipoprotein Accumulation in Patients with Diabetes Mellitus

Remnant lipoproteins are atherogenic and increased in patients with type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD) and other conditions. Thus far, information is limited regarding the synthesis and absorption of cholesterol in CKD patients and a possible link to the remnant levels. We examined possible alterations in serum markers of cholesterol synthesis and absorption and their potential associations with remnant lipoproteins in patients with CKD. The subjects included 146 consecutive patients with T2DM in various stages of CKD. We measured the levels of remnant lipoprotein cholesterol (RemL-C), lathosterol (a cholesterol synthesis marker) and campesterol (a cholesterol absorption marker). The urinary albumin to creatinine ratio (U-ACR) and estimated glomerular filtration rate (eGFR) were used to describe the degree of CKD. The median (interquartile range) levels of RemL-C, lathosterol and campesterol were 14.5 (11.5-23.4) mg/dL, 2.1 (1.7-2.9) μg/mL and 2.3 (1.7-3.0) μg/mL, respectively. The RemL-C level was positively correlated with the U-ACR and inversely correlated with the eGFR. The RemL-C level was positively correlated with both the lathosterol and campesterol levels. The lathosterol level was not significantly correlated with the U-ACR, although it was positively correlated with the eGFR. In contrast, the campesterol level was positively correlated with the ACR and inversely with the eGFR. In the multiple regression analysis, both lathosterol and campesterol were positively associated with the RemL-C level, independent of the U-ACR, eGFR and other variables. The serum campesterol concentrations are higher in patients with a greater degree of albuminuria and a lower renal funtion. In this study, the markers of cholesterol absorption and synthesis were independent determinants of the RemL-C level. Increased intestinal cholesterol absorption may be an additional mechanism for remnant accumulation in T2DM patients with CKD.

Association between cholesterol synthesis/absorption markers and effects of cholesterol lowering by atorvastatin among patients with high risk of coronary heart disease

No indices are currently available to facilitate clinicians to identify patients who need either statin monotherapy or statin-ezetimibe combined treatment. We aimed to investigate whether cholesterol synthesis and absorption markers can predict the cholesterol-lowering response to statin. Total 306 statin-naïve patients with high risk of coronary heart disease (CHD) were treated with atorvastatin 20 mg/day for 1 month. Cholesterol synthesis and absorption markers and LDL cholesterol (LDL-C) levels were measured before and after treatment. Atorvastatin decreased LDL-C by 36.8% (range: decrease of 74.5% to increase of 31.9%). Baseline cholesterol synthesis marker lathosterol and cholesterol absorption marker campesterol codetermined the effect of atorvastatin treatment. The effect of cholesterol lowering by atorvastatin was significantly associated with baseline lathosterol levels but modified bidirectionally by baseline campesterol levels. In patients with the highest baseline campesterol levels, atorvastatin treatment decreased cholesterol absorption by 46.1%, which enhanced the effect of LDL-C lowering. Atorvastatin treatment increased cholesterol absorption by 52.3% in those with the lowest baseline campesterol levels, which attenuated the effect of LDL-C reduction. Especially those with the highest lathosterol but the lowest campesterol levels at baseline had significantly less LDL-C reduction than those with the same baseline lathosterol levels but the highest campesterol levels (27.3% versus 42.4%, P = 0.002). These results suggest that combined patterns of cholesterol synthesis/absorption markers, rather than each single marker, are potential predictors of the LDL-C-lowering effects of atorvastatin in high-risk CHD patients.

GW24-e1865 Association between cholesterol synthesis/absorption markers and effects of cholesterol lowering by atorvastatin among patients with high risk of coronary heart disease

ObjectivesNo indices are available to facilitate clinicians to identify patients who need either statin monotherapy or statin-ezetimibe combined treatment. We aimed to test whether cholesterol synthesis and absorption markers can...

Cholesterol Metabolism After Bariatric Surgery in Grade 3 Obesity

OBJECTIVEMalabsorptive bariatric surgery (biliopancreatic diversion and biliointestinal bypass [BIBP]) reduces serum cholesterol levels more than restrictive surgery (adjustable gastric banding [AGB]), and this is thought to be due to greater weight loss. Our aim was to evaluate the changes of cholesterol metabolism induced by malabsorptive and restrictive surgery independent of weight loss.RESEARCH DESIGN AND METHODSIn a nonrandomized, self-selected, unblinded, active-comparator, bicenter, 6-month study, glucose metabolism (blood glucose and serum insulin levels and homeostasis model assessment of insulin resistance [HOMA-IR] index) and cholesterol metabolism (absorption: serum campesterol and sitosterol levels; synthesis: serum lathosterol levels; catabolism: rate of appearance and serum concentrations of serum 7-α- and serum 27-OH-cholesterol after infusions of deuterated 7-α- and 27-OH-cholesterol in sequence) were assessed in grade 3 obesity subjects undergoing BIBP (n = 10) and AGB (n = 10). Evaluations were performed before and 6 months after surgery.RESULTSSubjects had similar values at baseline. Weight loss was similar in the two groups of subjects, and blood glucose, insulin levels, HOMA-IR, and triglycerides decreased in a similar way. In contrast, serum cholesterol, LDL cholesterol, non-HDL cholesterol, serum sitosterol, and campesterol levels decreased and lathosterol levels increased only in BIBP subjects, not in AGB subjects. A significant increase in 7-α-OH-cholesterol occurred only with BIBP; serum 27-OH-cholesterol decreased in both groups.CONCLUSIONSMalabsorptive surgery specifically affects cholesterol levels, independent of weight loss and independent of glucose metabolism and insulin resistance. Decreased sterol absorption leads to decreased cholesterol and LDL cholesterol levels, accompanied by enhanced cholesterol synthesis and enhanced cholesterol catabolism. Compared with AGB, BIBP provides greater cholesterol lowering.

Change in cholesterol absorption and synthesis markers in patients with coronary heart disease after combination therapy with simvastatin plus ezetimibe

Background Statins and ezetimibe have been reported to change the balance of cholesterol metabolism, but few studies have been performed on Chinese patients. The aim of this study was to evaluate changes in cholesterol metabolism markers in patients with coronary heart disease. Methods Forty-five patients with coronary heart disease were treated with 20 mg/d of simvastatin for four weeks. Subjects were then divided into two different therapy groups according to whether they reached the target values for total cholesterol and low density lipoprotein cholesterol level. Patients who reached the target values remained on simvastatin and those who did not reach the target values took a combination of simvastatin plus 10 mg/d ezetimibe until the 12th week. The concentrations of cholesterol synthesis markers (lathosterol and desmosterol) and absorption markers (campesterol and sitosterol) were measured on the 1st, 4th, and 12th week of the study by gas chromatography. Results After treatment with simvastatin for four weeks, the levels of total cholesterol and low density lipoprotein cholesterol decreased significantly compared to levels measured during the 1st week (P <0.05). On the 12th week the levels of total cholesterol and low density lipoprotein cholesterol had decreased significantly (P <0.001) compared to levels during the 4th week. By the 12th week the levels of campesterol and sitosterol in the combination group had decreased significantly (P <0.05) compared with levels measured during the 4th week. Conclusions Coronary heart disease patients with high cholesterol synthesis at baseline might gain a greater benefit from simvastatin treatment. Combination therapy with simvastatin plus ezetimibe in patients with low cholesterol synthesis at baseline might increase the success rate of lipid-lowering through decreasing the absorption of cholesterol.

Dietary phytosterols modify the sterols and fatty acid profile in a tissue-specific pattern

Phytosterol consumption reduces the absorption of dietary cholesterol and can alter the tissue fatty acid composition. The effects of manipulating sterol and phospholipid fatty acid profile by increasing levels of phytosterols (1000 and 4000mg/kg diet) have been investigated in young Sprague–Dawley rats. Cholesterol levels decreased significantly only in liver, heart and skin. Significant increased levels of phytosterols were detected in all ten tissues analysed, with levels of campesterol in general being greater than those of β-sitosterol. The level of phytosterol incorporation ranged widely in tissues, more than doubling in heart, lung, spleen and erythrocytes to no significant increases in brain. In heart, kidney, spleen and lung there were dose dependent increases in phytosterol levels. The phospholipid fatty acid profile showed some small, but significant changes, but these were not consistent between tissues or for fatty acid classes. Dietary phytosterols accumulated differently in tissues and affected cholesterol levels and phospholipid fatty acid composition in a tissue-specific manner.

Role of the ABCG8 19H risk allele in cholesterol absorption and gallstone disease

BackgroundGallstone disease is associated with p.D19H of ABCG8 as well as alterations of cholesterol and bile acid metabolism. However, molecular mechanisms have not been fully elucidated. It is important to understand the link between the sterol transporters ABCG5/8 and NPC1L1 and intestinal cholesterol absorption as well as de novo synthesis in gallstone patients stratified according to 19H risk allele. Moreover, the functional importance of the 19H variant on intestinal ABCG8 feature remains to be clarified.MethodsMeasurements of serum surrogate markers of cholesterol absorption (plant sterols: sitosterol, campesterol) and synthesis (cholesterol precursor: lathosterol) were carried out by gas chromatography/mass spectrometry (GC/MS). For expression studies, total RNA was isolated from 168 ileal biopsies of study participants with (34) and without gallstone disease (134). Messenger RNA was measured by LightCycler real-time PCR. Genomic DNA was obtained from blood leukocytes. Genotype frequencies of p.D19H were established using MALDI-TOF mass spectrometry.ResultsCompared to controls, cholesterol absorption but not synthesis in gallstone carriers was diminished by about 21% based on low serum sitosterol (P = 0.0269) and campesterol (P = 0.0231) to cholesterol ratios. D19H was found to be significantly associated with gallstones (odds ratio [OR] = 2.9, P = 0.0220, 95% confidence interval [CI]:1.22-6.89), particularly in the overweight cohort (OR = 3.2, P = 0.0430, 95% CI:1.07-9.26). Cholesterol absorption was about 24% lower in individuals carrying p.D19H compared to wild type (Psitosterol = 0.0080, Pcampesterol = 0.0206). Moreover, irrespective of phenotype, carriers of p.D19H displayed a significant lower absorption than carriers of the major allele. The most pronounced effect on cholesterol absorption ratio was observed for serum campesterol levels (wild type controls to mutated controls 28%, P = 0.0347 and wild type controls to gallstone carriers with 19H allele 37%, P = 0.0030). Notably, ABCG5/8 and NPC1L1 expression was similar in gallstone carriers and controls regardless of p.D19H presence.ConclusionsBoth gallstone disease and p.D19H of ABCG8 are associated with diminished cholesterol absorption. However, p.D19H is not responsible for the differences in small intestinal sterol transporter expression.

The ABCG8 G574R Variant, Serum Plant Sterol Levels, and Cardiovascular Disease Risk in the Old Order Amish

To determine whether long-term exposure to moderate elevations in plasma plant sterol levels increases risk for atherosclerosis. In Old Order Amish participants aged 18 to 85 years, with (n=110) and without (n=181) 1 copy of the ABCG8 G574R variant, we compared mean plasma levels of plant sterols and cholesterol precursors and carotid intima-media wall thickness. Carriers of a single 574R allele had increased plant sterol levels (eg, 35%-37% higher plasma levels of sitosterol, campesterol, and stigmasterol) and increased plant sterol/cholesterol ratios (P<0.001 for all). 574R carriers had significantly decreased levels of lathosterol and lanosterol, precursors in a pathway for endogenous cholesterol synthesis, suggesting that plant sterols may alter regulation of genes involved in cholesterol synthesis. The G574R variant was not associated with high-density lipoprotein cholesterol or low-density lipoprotein cholesterol levels. Compared with noncarriers, 574R carriers had decreased carotid intima-media wall thickness (0.62 versus 0.66 mm; age- and sex-adjusted P=0.03). Adjustment for body weight, blood pressure, and standard lipid measures (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides) did not alter this association. Although the G574R variant is associated with moderately elevated plant sterol levels, carriers of the 574R allele had modestly lower levels of carotid wall thickness compared with noncarriers.

Cholesterol metabolism in acute upper gastrointestinal bleeding, preliminary observations

Hypocholesterolemia is commonly found in critically ill patients; however, the aetiology of this condition remains unclear. Several clinical studies refer to the possible negative impact of haemodilution on cholesterol (CH) metabolism in acute medical conditions. The aim of this study was to examine the serum CH profile (total CH, LDL and HDL CH) during acute gastrointestinal bleeding which is a life-threatening condition characterised by alterations in lipid metabolism. Serum non-CH sterols (lathosterol, squalene, sitosterol and campesterol) concentrations as markers of CH synthesis and CH absorption were measured at the same time. Twenty-four patients with acute upper gastrointestinal bleeding (UGIB) were measured for these parameters over a 6-day period. The control group was 100 healthy blood donors.We found lower plasma levels of total CH (p < 0.001) and LDL CH (p < 0.05) in patients with UGIB than in the control group. The decreased HDL CH plasma levels in patients were not statistically significant. In addition, patients had significantly lower plasma levels of lathosterol, squalene, campesterol and sitosterol (p < 0.05).Our results showed abnormalities not only in the CH plasma profile, but also in plasma concentrations of non-CH sterols. These findings of alterations in both the CH synthesis and absorption process could be a contributory cause of hypocholesterolemia during acute gastrointestinal bleeding. However, further research is necessary.

Dietary intake of plant sterols stably increases plant sterol levels in the murine brain

Plant sterols such as sitosterol and campesterol are frequently administered as cholesterol-lowering supplements in food. Recently, it has been shown in mice that, in contrast to the structurally related cholesterol, circulating plant sterols can enter the brain. We questioned whether the accumulation of plant sterols in murine brain is reversible. After being fed a plant sterol ester-enriched diet for 6 weeks, C57BL/6NCrl mice displayed significantly increased concentrations of plant sterols in serum, liver, and brain by 2- to 3-fold. Blocking intestinal sterol uptake for the next 6 months while feeding the mice with a plant stanol ester-enriched diet resulted in strongly decreased plant sterol levels in serum and liver, without affecting brain plant sterol levels. Relative to plasma concentrations, brain levels of campesterol were higher than sitosterol, suggesting that campesterol traverses the blood-brain barrier more efficiently. In vitro experiments with brain endothelial cell cultures showed that campesterol crossed the blood-brain barrier more efficiently than sitosterol. We conclude that, over a 6-month period, plant sterol accumulation in murine brain is virtually irreversible.

Abundant Pleiotropy in Human Complex Diseases and Traits

We present a systematic review of pleiotropy among SNPs and genes reported to show genome-wide association with common complex diseases and traits. We find abundant evidence of pleiotropy; 233 (16.9%) genes and 77 (4.6%) SNPs show pleiotropic effects. SNP pleiotropic status was associated with gene location (p = 0.024; pleiotropic SNPs more often exonic [14.5% versus 4.9% for nonpleiotropic, trait-associated SNPs] and less often intergenic [15.8% versus 23.6%]), "predicted transcript consequence" (p = 0.001; pleiotropic SNPs more often predicted to be structurally deleterious [5% versus 0.4%] but not more often in regulatory sequences), and certain disease classes. We develop a method to calculate the likelihood that pleiotropic links between traits occurred more often than expected and demonstrate that this approach can identify etiological links that are already known (such as between fetal hemoglobin and malaria risk) and those that are not yet established (e.g., between plasma campesterol levels and gallstones risk; and between immunoglobulin A and juvenile idiopathic arthritis). Examples of pleiotropy will accumulate over time, but it is already clear that pleiotropy is a common property of genes and SNPs associated with disease traits, and this will have implications for identification of molecular targets for drug development, future genetic risk-profiling, and classification of diseases.

Quality Characteristics and Antioxidants of Mavrolia cv. Virgin Olive Oil

AbstractThe quality characteristics and bioactive microconstituents of virgin olive oil produced by Mavrolia cv, an Olea europaea variety grown in Southern Peloponnesus, Greece, are reported for the first time. The oil samples of Mavrolia cv. studied fell within the limits established for the extra virgin olive oil (EVOO) category and were characterized by higher levels of campesterol (88.7 ± 14.8 vs. 56.1 ± 6.1 mg kg−1 oil) and β‐sitosterol (1692.6 ± 100.3 vs. 1356.2 ± 85 mg kg−1 oil) and relatively lower oxidative stability (19.35 ± 2.62 vs. 37.44 ± 1.97 h) compared to Koroneiki cv. The lower oxidative stability was positively correlated to significantly lower polyphenols (88.95 ± 2.33 vs. 233.75 ± 34.29) and α‐tocopherol (517.2 ± 6.50 vs. 655.37 ± 17.78) and to higher polyunsaturated fatty acids content (9.27 ± 0.35 vs. 6.41 ± 0.38). Tyrosol, ferulic acid and protocatechuic acid contents were significantly higher in Mavrolia cv. samples compared to Koroneiki cv. (218.80 ± 44.8 vs. 83.7 ± 23.1, 1.82 ± 0.11 vs. 0.97 ± 0.31, and 1.55 ± 0.39 vs. 0.35 ± 0.60 mg kg−1, respectively). Also, the bitter and pungent attributes were found in lower intensities compared to Koroneiki cv. EVOO for the same period (1.9 vs. 2.5 and 2.3 vs. 3.9, respectively). The ripe fruity intensity with walnut olfactory attribute of the Mavrolia cv., was also light to medium.

Comparison of the impact of trans fatty acids from ruminant and industrial sources on surrogate markers of cholesterol homeostasis in healthy men

Mechanisms by which trans fatty acids (TFA) from industrial (iTFA) and ruminant (rTFA) sources alter cholesterol homeostasis are virtually unknown. We compared the impact of dietary iTFA and rTFA on surrogate markers of cholesterol absorption (β-sitosterol and campesterol) and synthesis (lathosterol) in healthy men. In a randomized, controlled double-blind crossover study, 38 healthy men consumed three experimental isoenergetic diets for 4 wk each. The three diets were (i) high in iTFA (10.2 g/2500 kcal), (ii) high in rTFA (10.2 g/2500 kcal) and (iii) control diet low in TFA from any source (2.2 g/2500 kcal). The sum of plasma β-sitosterol and campesterol concentrations was significantly reduced after the iTFA diet compared with the control diet (-12%, p=0.050). The reduction in combined β-sitosterol and campesterol levels was larger in magnitude after the rTFA diet (-29% versus the control diet and -20% versus the iTFA diet, p<0.0001). The TFA-rich diets had no impact on plasma lathosterol concentrations. Very high intakes of rTFA and iTFA decrease cholesterol absorption but have no impact on cholesterol synthesis. Consumption of rTFA reduces cholesterol absorption to a greater extent than iTFA, but this difference does not ultimately affect plasma cholesterol concentrations.

Validation of an isotope dilution gas chromatography–mass spectrometry method for analysis of 7-oxygenated campesterol and sitosterol in human serum

High dose daily intake of plant sterols decreases the uptake of cholesterol in the intestine by competitive mechanisms and thus leads to reduced serum levels of total and LDL-cholesterol. By this, the commercialization of plant sterol enriched ‘functional food’ products is rapidly increasing. Subjects using these kinds of diet present a duplication of their serum plant sterol levels after long-term intake. In analogy to cholesterol, plant sterols such as campesterol and sitosterol can be oxidized to oxyphytosterols and these may counteract the primary anti-atherosclerotic action of cholesterol lowering. In order to investigate the whole spectrum of the consequences following high plant sterol intake a highly sensitive and specific isotope dilution gas chromatography–mass spectrometry method for the analysis of 7-oxygenated campesterol/sitosterol in trace amounts in human serum is presented in this paper. The validation was based on limits for detection and quantification, recovery, precision and minimization of autoxidation during work-up. Our results show an overall coefficient of variation ≤10% for the precision. The lowest limits for detection and quantification for 7α-hydroxy-campesterol were 7 pg/mL and 23 pg/mL, respectively. Data for overall sum recovery ranged from 92% to 115%. We practically used this method for analysis of oxyphytosterols simultaneously with plant sterol concentrations in serum from healthy volunteers. Sixteen subjects were treated with plant sterol enriched margarine (3 g/day) for 28 days. The results showed a significant increase of the oxyphytosterol 7β-hydroxy-sitosterol from 1.19 ± 0.54 (before intake) to 2.24 ± 1.24 ng/mL (mean ± SD; +86.7%; P = 0.007) after intake of the margarine. There was a highly significant correlation between the serum levels of campesterol and the sum of 7-oxygenated campesterol ( R 2 = 0.915; P < 0.001) and sitosterol and the sum of 7-oxygenated sitosterol ( R 2 = 0.915; P < 0.001). We can conclude from this study that the analytic method is well suited for detection of OPS, even at trace amounts.

Marked accumulation of 27-hydroxycholesterol in the brains of Alzheimer's patients with the Swedish APP 670/671 mutation

There is a significant flux of the neurotoxic oxysterol 27-hydroxycholesterol (27OHC) from the circulation across the blood-brain barrier. Because there is a correlation between 27OHC and cholesterol in the circulation and lipoprotein-bound cholesterol does not pass the blood-brain barrier, we have suggested that 27OHC may mediate the effects of hypercholesterolemia on the brain. We previously demonstrated a modest accumulation of 27OHC in brains of patients with sporadic Alzheimer's disease (AD), consistent with a role of 27OHC as a primary pathogenetic factor. We show here that there is a 4-fold accumulation of 27OHC in different regions of the cortexes of patients carrying the Swedish amyloid precursor protein (APPswe) 670/671 mutation. The brain levels of sitosterol and campesterol were not significantly different in the AD patients compared with the controls, suggesting that the blood-brain barrier was intact in the AD patients. We conclude that accumulation of 27OHC is likely to be secondary to neurodegeneration, possibly a result of reduced activity of CYP7B1, the neuronal enzyme responsible for metabolism of 27OHC. We discuss the possibility of a vicious circle in the brains of the patients with familial AD whereby neurodegenerative changes cause an accumulation of 27OHC that further accelerates neurodegeneration.