Dietary Phytosterols Research Articles

A Single Meal Containing Phytosterols Does Not Affect the Uptake or Tissue Distribution of Cholesterol in Zebrafish (Danio rerio)

Increased plant oil inclusion in aquaculture feeds has led to higher dietary phytosterol concentrations and speculation about whether this affects the metabolism and health of the fish. The mechanisms of cholesterol absorption and how phytosterols may affect this is unknown in fish. Zebrafish (Danio rerio) were used to study the effects of phytosterols on the uptake and organ distribution of dietary cholesterol in fish. One meal of diets containing a constant addition of cholesterol (cold and [4-14C] cholesterol) and varying types and concentrations of phytosterols were fed to fish in individual compartments. The fish were not previously conditioned on the experimental diets. Activity of 14C was then measured in water and fish tissues to quantify the tissue distribution and excretion of cholesterol. There were no effects of the moderate dietary concentrations of phytosterols on the excretion or tissue distribution of dietary cholesterol 24 hours after the meal.

Evaluation of β-Sitosterol Loaded PLGA and PEG-PLA Nanoparticles for Effective Treatment of Breast Cancer: Preparation, Physicochemical Characterization, and Antitumor Activity.

β-Sitosterol (β-Sit) is a dietary phytosterol with demonstrated anticancer activity against a panel of cancers, but its poor solubility in water limits its bioavailability and therapeutic efficacy. In this study, poly(lactide-co-glycolic acid) (PLGA) and block copolymers of poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) were used to encapsulate β-Sit into nanoparticles with the aim of enhancing its in vitro anticancer activity. β-Sitosterol-loaded PLGA and PEG-PLA nanoparticles (β-Sit-PLGA and β-Sit-PEG-PLA) were prepared by using a simple emulsion-solvent evaporation technique. The nanoparticles were characterized for size, particle size distribution, surface charge, and encapsulation efficiency. Their cellular uptake and antiproliferative activity was evaluated against MCF-7 and MDA-MB-231 human breast cancer cells using flow cytometry and MTT assays, respectively. β-Sit-PLGA and β-Sit-PEG-PLA nanoparticles were spherical in shape with average particle sizes of 215.0 ± 29.7 and 240.6 ± 23.3 nm, a zeta potential of −13.8 ± 1.61 and −23.5 ± 0.27 mV, respectively, and with narrow size distribution. The encapsulation efficiency of β-Sit was 62.89 ± 4.66 and 51.83 ± 19.72 % in PLGA and PEG-PLA nanoparticles, respectively. In vitro release in phosphate-buffered saline (PBS) and PBS/with 0.2% Tween 20 showed an initial burst release, followed by a sustained release for 408 h. β-Sit-PLGA nanoparticles were generally stable in a protein-rich medium, whereas β-Sit-PEG-PLA nanoparticles showed a tendency to aggregate. Flow cytometry analysis (FACS) indicated that β-Sit-PLGA nanoparticles were efficiently taken up by the cells in contrast to β-Sit-PEG-PLA nanoparticles. β-Sit-PLGA nanoparticles were therefore selected to evaluate antiproliferative activity. Cell viability was inhibited by up to 80% in a concentration range of 6.64–53.08 μg/mL compared to the untreated cells. Taken together, encapsulation of β-Sitosterol in PLGA nanoparticles is a promising strategy to enhance its anticancer activity against breast cancer cells.

Intake of stigmasterol and β-sitosterol alters lipid metabolism and alleviates NAFLD in mice fed a high-fat western-style diet

ObjectiveTo investigate and compare the effects of two common dietary phytosterols, stigmasterol and β-sitosterol, in altering lipid metabolism and attenuating nonalcoholic fatty liver disease (NAFLD). MethodsStigmasterol and β-sitosterol were administered to mice at 0.4% in a high-fat western-style diet (HFWD) for 17 weeks. ResultsStigmasterol and β-sitosterol significantly ameliorated HFWD-induced fatty liver and metabolic abnormalities, including elevated levels of hepatic total lipids, triacylglycerols, cholesterol and liver histopathology. Both phytosterols decreased the levels of intestinal bile acids, accompanied by markedly increased fecal lipid levels. In addition, they altered the expression of genes involved in lipid metabolism. β-Sitosterol was less effective in affecting most of these parameters. Lipidomic analysis of liver and serum samples showed that stigmasterol prevented the HFWD-induced elevation of some di- and triacylglycerol species and lowering of some phospholipid species. Stigmasterol also decreased serum levels of ceramides. ConclusionStigmasterol and β-sitosterol, at a dose corresponding to that suggested for humans by the FDA for lowering cholesterol levels, are shown to alleviate HFWD-induced NAFLD. Stigmasterol was more effective than β-sitosterol, possibly because of its suppression of hepatic lipogenic gene expression and modulation of circulating ceramide levels.

Associations of dietary phytosterols with blood lipid profiles and prevalence of obesity in Chinese adults, a cross-sectional study

BackgroundIt has been established in RCTs that high dose of phytosterols can significantly reduce blood cholesterol. However, it was uncertain whether low dose of phytosterols from daily diets was effective. In this study, we evaluated the associations between dietary phytosterols and body mass index (BMI), waist circumference (WC), blood glucose, serum lipid profiles and prevalence of overweight/obesity and abdominal obesity in healthy subjects.MethodsFour hundred nine men and 503 women aged 18–60 years were included in this study. Dietary intakes of phytosterols were estimated using a validated food frequency questionnaire. Height, body weight, WC and blood pressure were measured, an oral glucose tolerance test was performed. Moreover, fasting serum triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDLc) and low density lipoprotein cholesterol (LDLc) were further determined.ResultsWhen comparing extreme quartiles of dietary phytosterols, significant differences of BMI, WC, systolic blood pressure (SBP), diastolic blood pressure (DBP), serum TC and LDLc were found. Dietary phytosterols presented a negative association with BMI, WC, SBP, DBP, serum TC and LDLc (with and without adjustment for energy). After adjustment for confounders, we found higher dietary phytosterols were linked with lower prevalence of overweight/obesity (OR highest vs. lowest quartile = 0.487; 95% CI 0.234, 0.918 for men; OR highest vs. lowest quartile = 0.277; 95% CI 0.124, 0.619 for women) and abdominal obesity (OR highest vs. lowest quartile = 0.344; 95% CI 0.144, 0.819 for men; OR highest vs. lowest quartile = 0.321; 95% CI 0.140, 0.571 for women).ConclusionsHigher dietary phytosterols were associated with lower BMI, WC, blood pressure, serum TC and LDLc and lower prevalence of overweight/obesity and abdominal obesity in Chinese adults.

Feeding of phytosterols reduced testosterone production by modulating GnRH and GnIH expression in the brain and testes of male Japanese quail (Coturnix coturnix japonica)

Phytosterols (PS), or plant sterols used as cholesterol-lowering agents, have been shown to act as endocrine-disrupting chemicals in some laboratory animals. Moreover, dietary PS efficiently pass through the blood-brain barrier and accumulate in brain cell membranes. We asked whether the accumulation of PS affects reproduction through the hypothalamic-pituitary-gonadal axis. Thirty male quail chicks were randomly divided into 3 groups (control, 80mg/kg BW, and 800mg/kg BW), and daily single doses of PS or vehicle were gavaged into the crop sac from 15 to 100 d of age. At the end of the entire period, half of each group was injected intramuscularly with either 10μg of chicken gonadotropin-releasing hormone 1 (cGnRH-1) or phosphate-buffered saline solution (PBS) as the vehicle. Blood was collected before and 30min after cGnRH-1 challenge by jugular venipuncture and decapitation, respectively. The results indicated that testosterone concentrations were low (P <0.05) before (800mg/kg BW) and after GnRH challenge in PS-treated quails compared with controls (P <0.001). However, luteinizing hormone (LH) levels were not different among the groups before cGnRH-1 challenge. In addition, PS-gavaged animals failed to manifest increased LH levels after cGnRH-1 injection (P <0.01). The same trends were observed in pituitary LH levels at 800mg/kg BW PS after cGnRH-1 injection (P <0.05). Real-time PCR results revealed that PS (800mg/kg BW) feeding reduced expression of GnRH-1 in the brain and testes compared to controls. However, gonadotropin-inhibitory hormone (GnIH) expression was significantly elevated before and after GnRH-1 challenges in the brain and testes. Collectively, these results suggest that brain-mediated effects of PS on gonadal function occurs via the induction of GnIH gene expression, and these indirect effects are less potent than direct effects.

Tissue sterol composition in Atlantic salmon (Salmo salar L.) depends on the dietary cholesterol content and on the dietary phytosterol:cholesterol ratio, but not on the dietary phytosterol content.

The aim of the study was to investigate how the dietary sterol composition, including cholesterol, phytosterol:cholesterol ratio and phytosterols, affect the absorption, biliary excretion, retention, tissue storage and distribution of cholesterol and individual phytosterols in Atlantic salmon (Salmo salar L.). A feeding trial was conducted at two different temperatures (6 and 12°C), using nine different diets with varying contents of phytosterols, cholesterol and phytosterol:cholesterol ratio. Cholesterol retention values were clearly dependent on dietary cholesterol, and showed that fish fed cholesterol levels <1000 mg/kg feed produced considerable quantities of cholesterol de novo. Despite this production, cholesterol content increased with increasing dietary cholesterol in liver, plasma, bile, muscle, adipose tissue and whole fish at 12°C, and in plasma, bile and whole fish at 6°C. The tissue sterol composition generally depended on the dietary cholesterol content and on the dietary phytosterol:cholesterol ratio, but not on the dietary phytosterol content in itself. Campesterol and brassicasterol appeared to be the phytosterols with the highest intestinal absorption in Atlantic salmon. There was a high biliary excretion of campesterol, but not of brassicasterol, which accumulated in tissues and particularly in adipose tissue, with 2-fold-higher retention at 12°C compared with 6°C. Campesterol had the second highest retention of the phytosterols in the fish, but with no difference between the two temperatures. Other phytosterols had very low retention. Although brassicasterol retention decreased with increasing dietary phytosterols, campesterol retention decreased with increasing dietary cholesterol, indicating differences in the uptake mechanisms for these two sterols.

The Lipid-lowering Effects and Associated Mechanisms of Dietary Phytosterol Supplementation.

Phytosterols (PS) are plant-based structural analogous of mammalian cholesterol that have been shown to lower blood cholesterol concentrations by ~10%, although inter-individual response to PS supplementation due to subject-specific metabolic and genetic factors is evident. Recent work further suggests that PS may act as effective triglyceride (TG)-lowering agents with maximal TG reductions observed in hypertriglyceridemic subjects. Although PS have been demonstrated to interfere with cholesterol and perhaps TG absorption within the intestine, they also have the capacity to modulate the expression of lipid regulatory genes through liver X receptor (LXR) activation. Identification of single-nucleotide polymorphisms (SNP) in key cholesterol and TG regulating genes, in particular adenosine triphosphate binding cassette G8 (ABCG8) and apolipoprotein E (apoE) have provided insight into the potential of utilizing genomic identifiers as an indicator of PS responsiveness. While PS supplementation is deemed safe, expanding research into the atherogenic potential of oxidized phytosterols (oxyphytosterols) has emerged with their identification in arterial lesions. This review will highlight the lipid-lowering utility and associated mechanisms of PS and discuss novel applications and future research priorities for PS pertaining to in utero PS exposure for long-term cardiovascular disease risk protection and combination therapies with lipidlowering drugs.

Improved fruit α-tocopherol, carotenoid, squalene and phytosterol contents through manipulation of Brassica juncea 3-HYDROXY-3-METHYLGLUTARYL-COA SYNTHASE1 in transgenic tomato.

Summary3‐Hydroxy‐3‐methylglutaryl‐coenzyme A synthase (HMGS) in the mevalonate (MVA) pathway generates isoprenoids including phytosterols. Dietary phytosterols are important because they can lower blood cholesterol levels. Previously, the overexpression of Brassica juncea wild‐type (wt) and mutant (S359A) BjHMGS1 in Arabidopsis up‐regulated several genes in sterol biosynthesis and increased sterol content. Recombinant S359A had earlier displayed a 10‐fold higher in vitro enzyme activity. Furthermore, tobacco HMGS overexpressors (OEs) exhibited improved sterol content, plant growth and seed yield. Increased growth and seed yield in tobacco OE‐S359A over OE‐wtBjHMGS1 coincided with elevations in NtSQS expression and sterol content. Herein, the overexpression of wt and mutant (S359A) BjHMGS1 in a crop plant, tomato (Solanum lycopersicum), caused an accumulation of MVA‐derived squalene and phytosterols, as well as methylerythritol phosphate (MEP)‐derived α‐tocopherol (vitamin E) and carotenoids, which are important to human health as antioxidants. In tomato HMGS‐OE seedlings, genes associated with the biosyntheses of C10, C15 and C20 universal precursors of isoprenoids, phytosterols, brassinosteroids, dolichols, methylerythritol phosphate, carotenoid and vitamin E were up‐regulated. In OE‐S359A tomato fruits, increased squalene and phytosterol contents over OE‐wtBjHMGS1 were attributed to heightened SlHMGR2, SlFPS1, SlSQS and SlCYP710A11 expression. In both tomato OE‐wtBjHMGS1 and OE‐S359A fruits, the up‐regulation of SlGPS and SlGGPPS1 in the MEP pathway that led to α‐tocopherol and carotenoid accumulation indicated cross‐talk between the MVA and MEP pathways. Taken together, the manipulation of BjHMGS1 represents a promising strategy to simultaneously elevate health‐promoting squalene, phytosterols, α‐tocopherol and carotenoids in tomato, an edible fruit.

Phytosterol-mediated inhibition of intestinal cholesterol absorption is independent of liver X receptor

Aim: The evidence supporting the hypothesis that phytosterols act as ligands for LXRs is contradictory. A clear assessment of this hypothesis requires the use of LXRab-deficient animals. Therefore, the aim of the present study was to examine the effects of dietary phytosterol supplementation on intestinal cholesterol absorption and fecal neutral sterol excretion in wild-type and LXRab-deficient mice, as well as the effects of the combined administration of phytosterols and LXRab agonists.

Phytosterols on growth performance, antioxidant enzymes and intestinal morphology in weaned piglets.

Plant extracts have been used widely to improve growth, lower cholesterol, and exert antioxidative defense and antimicrobial activities in animal production. The present study aimed to investigate the effects of dietary phytosterols (PS) on growth performance, antioxidant enzymes and intestinal morphology in weaned piglets. A total of 120 crossbred piglets, weighing 9.58 ± 0.26 kg, were randomly allocated to three treatments: control, PS (0.2 g kg-1 ) and polymyxin E (0.04 g kg-1 , antibiotic control). Compared to the control, PS or polymyxin E supplementation decreased diarrhea rate, serum cholesterol and malondialdehyde (MDA) of the piglets (P < 0.05). Liver MDA was significantly decreased in PS-fed piglets compared to the control (P < 0.05), although there was no difference between the control and polymyxin E-fed piglets. PS increased the villous height/crypt depth ratio of the duodenum and jejunum compared to the control (P < 0.05). Polymyxin E supplementation in piglets did not alter the villous height/crypt depth ratio but raised the villous height and crypt depth of the duodenum compared to the control (P < 0.05). The results of the present study indicated that PS could decrease diarrhea rate, lower serum cholesterol, reduce lipid peroxidation and ameliorate intestinal morphology in weaned piglets. In addition, PS exerted better amelioration on intestinal morphology than polymyxin E in piglets. © 2017 Society of Chemical Industry.

English

Malnutrition is the major problem in many countries of the world including Pakistan. Due to inadequate macro and micro nutrients, prevalence of diseases is increasing day by day. Haleem is a common diet that can be used by people of all age group. It is prepared by different methods and consists of Lens culinaris L., Hordeum vulgare L., Phaseolus vulgaris L., Vigna mungo L., Vigna radiate L., Cicer arietinum L., Oryza sativa L., Triticum aestivum L., Gallus gallus domesticus, Brassica napus L., Zingiber officinale Rosec., Curcuma longa L., Allium sativum L., Allium cepa L., Capsicum annuum L., Cinnamomum zeylanicum L., Cuminum cyminum L., Myristica fragrans Houtt, Piper longum L., Mentha piperita L., Amomum subulatum Roxb., Coriandrum sativum L., Mangifera indica L., Citrus lemon L. and rock salt. These materials either from plant, animal and mineral origin contain variety of substances such as dietary fibers, energy, proteins, carbohydrates, lignins, tannins, flavonoids, phytosterols, squalene, tocopherols, saponins, pre-biotics, plant acids, sterol, crude fibre, fats, vitamin and minerals. Key words: Neurological disorder, nutrition, micronutrients, macronutrients, bioactive compounds.

Phytosterol-mediated inhibition of intestinal cholesterol absorption in mice is independent of liver X receptor.

Previous studies have proposed that phytosterols activate liver X receptors (LXR) in the intestine, thereby reducing intestinal cholesterol absorption and promoting fecal cholesterol excretion. In the present study, we examined the effects of dietary phytosterol supplementation on intestinal cholesterol absorption and fecal neutral sterol excretion in LXRαβ-deficient mice, and wild-type mice treated with synthetic high-affinity LXRαβ agonists. LXRαβ deficiency led to an induction of intestinal cholesterol absorption and liver cholesterol accumulation. Phytosterol feeding resulted in an approximately 40% reduction of intestinal cholesterol absorption both in wild-type and LXRαβ-deficient mice, reduced dietary cholesterol accumulation in liver and promoted the excretion of fecal cholesterol-derived compounds. Furthermore, phytosterols produced additive inhibitory effects on cholesterol absorption in mice treated with LXRαβ agonists. Our data confirm the effect of LXR in regulating intestinal cholesterol absorption and demonstrate that the cholesterol-lowering effects of phytosterols occur in an LXR-independent manner.

Association between phytosterol intake and colorectal cancer risk: a case-control study.

A study in rodent models showed that phytosterols protected against colon carcinogenesis, probably by inhibiting dysregulated cell cycle progression and inducing cellular apoptosis. However, epidemiological studies on the relationship between phytosterols and colorectal cancer risk are quite limited. The aim of this study was to investigate dietary phytosterol intake in relation to colorectal cancer risk in the Chinese population. A case-control study was conducted from July 2010 to June 2016, recruiting 1802 eligible colorectal cancer cases plus 1813 age (5-year interval) and sex frequency-matched controls. Dietary information was collected by using a validated FFQ. The OR and 95 % CI of colorectal cancer risk were assessed by multivariable logistic regression models. A higher total intake of phytosterols was found to be associated with a 50 % reduction in colorectal cancer risk. After adjusting for various confounders, the OR of the highest quartile intake compared with the lowest quartile intake was 0·50 (95 % CI 0·41, 0·61, P trend<0·01) for total phytosterols. An inverse association was also found between the consumption of β-sitosterol, campesterol, campestanol and colorectal cancer risk. However, stigmasterol intake was related to an increased risk of colorectal cancer. No statistically significant association was found between β-sitostanol and colorectal cancer risk. Stratified analysis by sex showed that the positive association of stigmasterol intake with colorectal cancer risk was found only in women. These data indicated that the consumption of total phytosterols, β-sitosterol, campesterol and campestanol is inversely associated with colorectal cancer risk in a Chinese population.

Dietary phytosterols intakes are inversely associated with colorectal cancer risk among Chinese population

ObjectiveAccording to the previous studies based on rodent models, phytosterols provided protection against colon carcinogenesis probably by inhibiting dysregulated cell cycle progression and inducing apoptosis. However, epidemiological studies on the relationship between phytosterols and colorectal cancer risk were quite limited. The aim of this study was to investigate the association between dietary phytosterols intakes and colorectal cancer risk among Chinese population.MethodsA case‐control study of 1363 consecutively recruited colorectal cancer cases and 1363 frequency‐matched controls (age and sex) was conducted from July 2010 to May 2015 in Guangzhou, China. Dietary information was collected by using a validated interviewer‐administered food frequency questionnaire. Five subclasses of phytosterols (β‐sitosterol, campesterol, β‐sitostanol, campestanol and stigmasterol) were obtained from food content according to the Chinese Food Composition Table. The odds ratios (ORs) and 95% confidence intervals (95% CIs) of colorectal cancer risk were assessed by multivariate logistic regression models after adjusting for various potential confounders.ResultsAn inverse association was found between the consumption of β‐sitosterol, campesterol, β‐sitostanol, campestanol and total sterols and colorectal cancer risk. After adjusting various confounders, ORs of the highest quartile compared with the lowest quartile intake were 0.44 (95% CIs 0.35–0.56, Ptrend &lt; 0.01) for β‐sitosterol, 0.56 (95% CIs 0.45–0.71, Ptrend &lt; 0.01) for campesterol, 0.58 (95% CIs 0.46–0.73, Ptrend &lt; 0.01) for β‐sitostanol, 0.60 (95% CIs 0.48–0.76, Ptrend &lt; 0.01) for campestanol and 0.50 (95% CIs 0.40–0.63, Ptrend &lt; 0.01) for total sterols, respectively. No significant association was observed between stigmasterol intake and colorectal cancer risk. Subgroup analysis by cancer site showed that the inverse associations between β‐sitosterol, campesterol, β‐sitostanol and campestanol and total sterols intakes and colorectal cancer risk were observed in both colon and rectal cancer sites. Stratified analysis by sex showed that dietary intakes of β‐sitosterol, campesterol, stigmasterol, β‐sitostanol, campestanol and total sterols were inversely associated with colorectal cancer risk among men. There was no significant inverse association between consumption of any of the phytosterols and colorectal cancer risk among women. However, stigmasterol intake was positively associated with colorectal cancer risk among women.ConclusionConsumption of β‐sitosterol, campesterol, stigmasterol β‐sitostanol and campestanol was inversely associated with colorectal cancer risk. No significant association was observed between stigmasterol intake and colorectal cancer risk.Support or Funding InformationThis study was supported by Guangdong Natural Science Foundation (No: 2014A030313188).

Bioconversion of 13C-labeled microalgal phytosterols to cholesterol by the Northern Bay scallop, Argopecten irradians irradians

Bivalve mollusks lack de novo cholesterol biosynthesis capabilities and therefore rely upon dietary sources of sterols for rapid growth. Microalgae that constitute the main source of nutrition for suspension-feeding bivalves contain a diverse array of phytosterols, in most cases lacking cholesterol. Rapid growth of bivalves on microalgal diets with no cholesterol implies that some phytosterols can satisfy the dietary requirement for cholesterol through metabolic conversion to cholesterol, but such metabolic pathways have not been rigorously demonstrated. In the present study, stable isotope-labeled phytosterols were used to supplement a unialgal diet of Rhodomonas sp. and their biological transformation to cholesterol within scallop tissues was determined using (13)C-NMR spectroscopy. Scallops efficiently dealkylated ∆(5) C29 (24-ethyl) sterols to cholesterol, and the only C28 sterol that was dealkylated efficiently possessed the 24(28)-double bond. Non-metabolized dietary phytosterols accumulated in the soft tissues. Observed formation of ∆(5,7) sterols (provitamin D) from ∆(5) sterols may represent initiation of steroid hormone (possibly ecdysone) biosynthesis. These findings provide a key component necessary for formulation of nutritionally complete microalgal diets for hatchery production of seed for molluscan aquaculture.

The Progressive BSSG Rat Model of Parkinson's: Recapitulating Multiple Key Features of the Human Disease.

The development of effective neuroprotective therapies for Parkinson's disease (PD) has been severely hindered by the notable lack of an appropriate animal model for preclinical screening. Indeed, most models currently available are either acute in nature or fail to recapitulate all characteristic features of the disease. Here, we present a novel progressive model of PD, with behavioural and cellular features that closely approximate those observed in patients. Chronic exposure to dietary phytosterol glucosides has been found to be neurotoxic. When fed to rats, β-sitosterol β-d-glucoside (BSSG) triggers the progressive development of parkinsonism, with clinical signs and histopathology beginning to appear following cessation of exposure to the neurotoxic insult and continuing to develop over several months. Here, we characterize the progressive nature of this model, its non-motor features, the anatomical spread of synucleinopathy, and response to levodopa administration. In Sprague Dawley rats, chronic BSSG feeding for 4 months triggered the progressive development of a parkinsonian phenotype and pathological events that evolved slowly over time, with neuronal loss beginning only after toxin exposure was terminated. At approximately 3 months following initiation of BSSG exposure, animals displayed the early emergence of an olfactory deficit, in the absence of significant dopaminergic nigral cell loss or locomotor deficits. Locomotor deficits developed gradually over time, initially appearing as locomotor asymmetry and developing into akinesia/bradykinesia, which was reversed by levodopa treatment. Late-stage cognitive impairment was observed in the form of spatial working memory deficits, as assessed by the radial arm maze. In addition to the progressive loss of TH+ cells in the substantia nigra, the appearance of proteinase K-resistant intracellular α-synuclein aggregates was also observed to develop progressively, appearing first in the olfactory bulb, then the striatum, the substantia nigra and, finally, hippocampal and cortical regions. The slowly progressive nature of this model, together with its construct, face and predictive validity, make it ideal for the screening of potential neuroprotective therapies for the treatment of PD.

Effects of dietary phytosterol concentration on performance, egg quality and cholesterol content in laying hens

Effects of dietary phytosterol concentration on performance, egg quality and cholesterol content in laying hens

Natural Dietary Phytosterols.

Most clinical phytosterol studies are performed by adding purified supplements to smaller phytosterol amounts present in the natural diet. However, natural dietary phytosterols themselves may also have important effects on cholesterol metabolism. Epidemiological work using food frequency questionnaires to estimate dietary intake suggest that extremes of normal consumption may be associated with 3-14% changes in LDL cholesterol. Standardized food databases do not have enough phytosterol values to allow calculation of phytosterol intake for individuals outside of specialized studies. Natural diets contain phytosterol amounts ranging from less than 60 mg/2000 kcal to over 500 mg/2000 kcal. Physiological studies in which whole body cholesterol metabolism is investigated show large effects of natural dietary phytosterols on cholesterol absorption efficiency, cholesterol biosynthesis and cholesterol excretion which exceed the magnitude of changes in LDL cholesterol. The dual effects of natural phytosterols on both LDL-C and whole body cholesterol metabolism need to be considered in relating them to potential protection from coronary heart disease risk.

Lipidomic changes of LDL in overweight and moderately hypercholesterolemic subjects taking phytosterol- and omega-3-supplemented milk

The benefits of dietary phytosterols (PhySs) and long-chain n-3 PUFA (ω3) have been linked to their effects as cholesterol- and triglyceride (TGL)-lowering agents. However, it remains unknown whether these compounds have further metabolic effects on LDL lipid composition. Here, we studied the effects of PhyS- or ω3-supplemented low-fat milk (milk) on the LDL-lipidome. Overweight and moderately hypercholesterolemic subjects (n = 32) were enrolled in a two-arm longitudinal crossover study. Milk (250 ml/day), enriched with either 1.57 g PhyS or 375 mg ω3 (EPA + DHA), was given to the participants during two sequential 28 day intervention periods. Compared with baseline, PhyS-milk induced a higher reduction in the LDL cholesterol (LDLc) level than ω3-milk. LDL resistance to oxidation was significantly increased after intervention with PhyS-milk. Changes in TGL and VLDL cholesterol were only evident after ω3-milk intake. Lipidomic analysis revealed a differential effect of the PhyS- and ω3-milk interventions on the LDL lipid metabolite pattern. Content in LDL-glycerophospholipids was reduced after PhyS-milk intake, with major changes in phosphatidylcholine (PC) and phosphatidylserine subclasses, whereas ω3-milk induced significant changes in the long-chain polyunsaturated cholesteryl esters and in the ratio PC36:5/lysoPC16:0, associated to a reduced inflammatory activity. In conclusion, daily intake of milk products containing PhyS or ω3 supplements induce changes in the LDL-lipidome that indicate reduced inflammatory and atherogenic effects, beyond their LDLc- and TGL-lowering effects.

Plasma biomarker of dietary phytosterol intake.

BackgroundDietary phytosterols, plant sterols structurally similar to cholesterol, reduce intestinal cholesterol absorption and have many other potentially beneficial biological effects in humans. Due to limited information on phytosterol levels in foods, however, it is difficult to quantify habitual dietary phytosterol intake (DPI). Therefore, we sought to identify a plasma biomarker of DPI.Methods and FindingsData were analyzed from two feeding studies with a total of 38 subjects during 94 dietary periods. DPI was carefully controlled at low, intermediate, and high levels. Plasma levels of phytosterols and cholesterol metabolites were assessed at the end of each diet period. Based on simple ordinary least squares regression analysis, the best biomarker for DPI was the ratio of plasma campesterol to the endogenous cholesterol metabolite 5-α-cholestanol (R2 = 0.785, P < 0.0001). Plasma campesterol and 5-α-cholestanol levels varied greatly among subjects at the same DPI level, but were positively correlated at each DPI level in both studies (r > 0.600; P < 0.01).ConclusionThe ratio of plasma campesterol to the coordinately regulated endogenous cholesterol metabolite 5-α-cholestanol is a biomarker of dietary phytosterol intake. Conversely, plasma phytosterol levels alone are not ideal biomarkers of DPI because they are confounded by large inter-individual variation in absorption and turnover of non-cholesterol sterols. Further work is needed to assess the relation between non-cholesterol sterol metabolism and associated cholesterol transport in the genesis of coronary heart disease.