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1.
Molecules ; 25(11)2020 May 27.
Article in English | MEDLINE | ID: mdl-32471050

ABSTRACT

Plant seeds have been found to contain bioactive compounds that have potential nutraceutical benefits. Guava seeds (Psidium guajava) are by-products in the beverage and juice industry; however, they can be utilized for a variety of commercial purposes. This study was designed to analyze the phytochemicals of the n-hexane extract of guava seed oil (GSO), to study its free-radical scavenging activity, and to monitor the changes in serum lipids and fatty acid profiles in rats that were fed GSO. The GSO was analyzed for phytochemicals using chromatographic methods. It was also tested for free-radical scavenging activity in hepatoma and neuroblastoma cells, and analyzed in terms of serum lipids and fatty acids. GSO was found to contain phenolic compounds (e.g., chlorogenic acid and its derivatives) and phytosterols (e.g., stimasterol, ß-sitosterol and campesterol), and exerted radical-scavenging activity in cell cultures in a concentration-dependent manner. Long-term consumption of GSO did not increase cholesterol and triglyceride levels in rat serum, but it tended to decrease serum fatty acid levels in a concentration-dependent manner. This is the first study to report on the lipid, phytosterol and phenolic compositions, antioxidant activity, and the hepato- and neuro-protection of hydrogen peroxide-induced oxidative stress levels in the GSO extract.


Subject(s)
Phenols/blood , Phytosterols/blood , Plant Oils/chemistry , Psidium/chemistry , Seeds/chemistry , Animals , Antioxidants/metabolism , Carcinoma, Hepatocellular/blood , Cholesterol/analogs & derivatives , Cholesterol/blood , Female , Hexanes/chemistry , Liver Neoplasms/blood , Male , Oxidative Stress/drug effects , Plant Extracts/chemistry , Plant Extracts/pharmacology , Rats , Sitosterols/blood , Triglycerides/blood
2.
Sci Rep ; 7(1): 15288, 2017 11 10.
Article in English | MEDLINE | ID: mdl-29127425

ABSTRACT

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.


Subject(s)
Diabetes Mellitus, Type 2 , Glucose Intolerance , Oxidative Stress/drug effects , Sitosterols/blood , Thioctic Acid/administration & dosage , Vitamin E/administration & dosage , Adolescent , Adult , Aged , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/drug therapy , Female , Glucose Intolerance/blood , Glucose Intolerance/drug therapy , Humans , Male , Middle Aged
3.
JPEN J Parenter Enteral Nutr ; 41(6): 1014-1022, 2017 08.
Article in English | MEDLINE | ID: mdl-26962062

ABSTRACT

BACKGROUND: Parenteral plant sterols (PSs) are considered hepatotoxic; however, liver PSs and their associations with liver injury in patients with intestinal failure (IF) have not been reported. MATERIALS AND METHODS: We analyzed liver and serum PS (avenasterol, campesterol, sitosterol, and stigmasterol) concentrations and ratios to cholesterol and their associations with biochemical and histologic liver damage in children with IF during (n = 7) parenteral nutrition (PN) and after weaning off it (n = 9), including vegetable oil-based lipid emulsions. RESULTS: Liver avenasterol, sitosterol, and total PS concentrations and cholesterol ratios were 2.4-fold to 5.6-fold higher in PN-dependent patients ( P < .05). Parenteral PS delivery reflected liver avenasterol and sitosterol ratios to cholesterol ( r = 0.83-0.89, P = .02-.04), while serum and liver total PS levels were positively interrelated ( r = 0.98, P < .01). Any liver histopathology was equally common while portal inflammation more frequent (57 vs 0%, P = .02) in PN-dependent patients. All liver PS fractions correlated positively with histologic portal inflammation ( r = 0.53-0.66, P < .05), and their total concentration was significantly ( P = .01) higher among patients with versus without portal inflammation. In PN-dependent patients, liver fibrosis and any histopathology correlated with liver campesterol and stigmasterol levels ( r = 0.79-0.87, P ≤ .03). CONCLUSION: Among children with IF, parenteral PSs accumulate in the liver, reflect their increased serum levels, and relate with biochemical liver injury, portal inflammation, and liver fibrosis, thus supporting their role in promoting liver damage.


Subject(s)
Inflammation/blood , Intestinal Diseases/therapy , Liver/drug effects , Parenteral Nutrition/adverse effects , Phytosterols/adverse effects , Phytosterols/blood , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Chemical and Drug Induced Liver Injury/blood , Child , Child, Preschool , Cholesterol/analogs & derivatives , Cholesterol/blood , Female , Humans , Infant , Intestinal Diseases/complications , Liver/physiopathology , Male , Plant Oils/administration & dosage , Plant Oils/adverse effects , Portal Vein/pathology , Sitosterols/blood , Stigmasterol/blood , Triglycerides/blood , gamma-Glutamyltransferase/blood
4.
Eur J Nutr ; 55(3): 1283-96, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26058880

ABSTRACT

PURPOSE: The contribution of extra virgin olive oil (EVOO) macro- and micro-constituents in heart oxidative and inflammatory status in a hypercholesterolemic rat model was evaluated. Fatty acid profile as well as α-tocopherol, sterol, and squalene content was identified directly in rat hearts to distinguish the effect of individual components or to enlighten the potential synergisms. METHODS: Oils and oil-products with discernible lipid and polar phenolic content were used. Wistar rats were fed a high-cholesterol diet solely, or supplemented with one of the following oils, i.e., EVOO, sunflower oil (SO), and high-oleic sunflower oil (HOSO) or oil-products, i.e., phenolics-deprived EVOO [EVOO(-)], SO enriched with the EVOO phenolics [SO(+)], and HOSO enriched with the EVOO phenolics [HOSO(+)]. Dietary treatment lasted 9 weeks; at the end of the intervention blood and heart samples were collected. RESULTS: High-cholesterol-diet-induced dyslipidemia was shown by increase in serum total cholesterol, low-density lipoprotein cholesterol, and triacylglycerols. Dyslipidemia resulted in increased malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) levels, while glutathione and interleukin 6 levels remained unaffected in all intervention groups. Augmentation observed in MDA and TNF-α was attenuated in EVOO, SO(+), and HOSO(+) groups. Heart squalene and cholesterol content remained unaffected among all groups studied. Heart α-tocopherol was determined by oil α-tocopherol content. Variations were observed for heart ß-sitosterol, while heterogeneity was reported with respect to heart fatty acid profile in all intervention groups. CONCLUSIONS: Overall, we suggest that the EVOO-polar phenolic compounds decreased MDA and TNF-α in hearts of cholesterol-fed rats.


Subject(s)
Diet, High-Fat/adverse effects , Hypercholesterolemia/blood , Inflammation/blood , Olive Oil/pharmacology , Oxidative Stress , Animals , Cholesterol, Dietary/administration & dosage , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Diet , Dyslipidemias/diet therapy , Dyslipidemias/etiology , Fatty Acids/blood , Glutathione/blood , Interleukin-6/blood , Male , Malondialdehyde/blood , Phenols/analysis , Phenols/pharmacology , Plant Oils/pharmacology , Rats , Rats, Wistar , Sitosterols/blood , Sunflower Oil , Triglycerides/blood , Tumor Necrosis Factor-alpha/blood , alpha-Tocopherol/blood
5.
J Clin Lipidol ; 9(4): 542-52, 2015.
Article in English | MEDLINE | ID: mdl-26228672

ABSTRACT

OBJECTIVE: Plant sterol (PS) supplementation has been widely used alone or combined with lipid-lowering therapies (LLTs) to reduce low-density lipoprotein (LDL) cholesterol. The effects of PS added to high-intensity LLT are less reported, especially regarding the effects on cholesterol synthesis and absorption. METHODS: A prospective, randomized, open-label study, with parallel arms and blinded end points was designed to evaluate the effects of addition of PS to LLT on LDL cholesterol, markers of cholesterol synthesis, and absorption. Eighty-six patients of both genders were submitted to a 4-wk run-in period with atorvastatin 10 mg (baseline). Following, subjects received atorvastatin 40 mg, ezetimibe 10 mg, or combination of both drugs for another 4-wk period (phase I). In phase II, capsules containing 2.0 g of PSs were added to previous assigned treatments for 4 wk. Lipids, apolipoproteins, plasma campesterol, ß-sitosterol, and desmosterol levels were assayed at all time points. Within and between-group analyses were performed. RESULTS: Compared with baseline, atorvastatin 40 mg reduced total and LDL cholesterol (3% and 22%, respectively, P < .05), increased ß-sitosterol, campesterol/cholesterol, and ß-sitosterol/cholesterol ratios (39%, 47%, and 32%, respectively, P < .05); ezetimibe 10 mg reduced campesterol and campesterol/cholesterol ratio (67% and 70%, respectively, P < .05), and the combined therapy decreased total and LDL cholesterol (22% and 38%, respectively, P < .05), campesterol, ß-sitosterol, and campesterol/cholesterol ratio (54%, 40%, and 27%, P < .05). Addition of PS further reduced total and LDL cholesterol by ∼ 7.7 and 6.5%, respectively, in the atorvastatin therapy group and 5.0 and 4.0% in the combined therapy group (P < .05, for all), with no further effects in absorption or synthesis markers. CONCLUSIONS: PS added to LLT can further improve lipid profile, without additional effects on intestinal sterol absorption or synthesis.


Subject(s)
Anticholesteremic Agents/administration & dosage , Dietary Supplements , Hypercholesterolemia/drug therapy , Phytosterols/administration & dosage , Aged , Apolipoproteins/blood , Atorvastatin/administration & dosage , Cholesterol/analogs & derivatives , Cholesterol/blood , Cholesterol, LDL/blood , Drug Synergism , Ezetimibe/administration & dosage , Ezetimibe/adverse effects , Female , Humans , Hypercholesterolemia/blood , Lipid Metabolism/drug effects , Lipids/blood , Male , Middle Aged , Phytosterols/adverse effects , Phytosterols/blood , Sitosterols/blood
6.
Br J Nutr ; 112(5): 744-52, 2014 Sep 14.
Article in English | MEDLINE | ID: mdl-25008473

ABSTRACT

A randomised, cross-over, controlled-feeding study was conducted to evaluate the cholesterol-lowering effects of diets containing pistachios as a strategy for increasing total fat (TF) levels v. a control (step I) lower-fat diet. Ex vivo techniques were used to evaluate the effects of pistachio consumption on lipoprotein subclasses and functionality in individuals (n 28) with elevated LDL levels ( ≥ 2·86 mmol/l). The following test diets (SFA approximately 8 % and cholesterol < 300 mg/d) were used: a control diet (25 % TF); a diet comprising one serving of pistachios per d (1PD; 30 % TF); a diet comprising two servings of pistachios per d (2PD; 34 % TF). A significant decrease in small and dense LDL (sdLDL) levels was observed following the 2PD dietary treatment v. the 1PD dietary treatment (P= 0·03) and following the 2PD dietary treatment v. the control treatment (P= 0·001). Furthermore, reductions in sdLDL levels were correlated with reductions in TAG levels (r 0·424, P= 0·025) following the 2PD dietary treatment v. the control treatment. In addition, inclusion of pistachios increased the levels of functional α-1 (P= 0·073) and α-2 (P= 0·056) HDL particles. However, ATP-binding cassette transporter A1-mediated serum cholesterol efflux capacity (P= 0·016) and global serum cholesterol efflux capacity (P= 0·076) were only improved following the 2PD dietary treatment v. the 1PD dietary treatment when baseline C-reactive protein status was low ( < 103µg/l). Moreover, a significant decrease in the TAG:HDL ratio was observed following the 2PD dietary treatment v. the control treatment (P= 0·036). There was a significant increase in ß-sitosterol levels (P< 0·0001) with the inclusion of pistachios, confirming adherence to the study protocol. In conclusion, the inclusion of pistachios in a moderate-fat diet favourably affects the cardiometabolic profile in individuals with an increased risk of CVD.


Subject(s)
Cardiovascular Diseases/prevention & control , Dietary Fats/administration & dosage , Lipoproteins, LDL/blood , Metabolic Syndrome/prevention & control , Nuts , Pistacia , Anticholesteremic Agents/administration & dosage , Biomarkers/blood , C-Reactive Protein/analysis , Cardiovascular Diseases/blood , Cholesterol/blood , Cross-Over Studies , Female , Humans , Insulin Resistance , Lipoproteins/blood , Male , Metabolic Syndrome/blood , Middle Aged , Nuts/chemistry , Phytosterols/administration & dosage , Phytotherapy , Sitosterols/blood , Triglycerides/blood
7.
Nutr Metab Cardiovasc Dis ; 24(10): 1090-6, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24909799

ABSTRACT

BACKGROUND AND AIM: Post-menopausal women are at higher risk of cardiovascular disease and bone demineralization. Phytosterols (PS) may be used for hypercholesterolemia in some groups and ß-cryptoxanthin (ß-Cx) displays a unique anabolic effect on bone. Our aim was to assess the changes in cardiovascular and bone turnover markers from the oral intake of ß-Cx and PS in post-menopausal women. METHODS AND RESULTS: A randomized, double-blind, crossover study with ß-Cx (0.75 mg/day) and PS (1.5 g/day), single and combined, was performed in 38 postmenopausal women. Diet was supplemented with 1 × 250 mL milk-based fruit drink/day for 4 weeks with a wash-out period of 4-weeks in between. Serum ß-Cx and PS were determined by UPLC and CG-FID respectively. Outcome variables included markers of bone turnover and cardiovascular risk. Biological effect was assessed by paired t test and generalized estimating equations analysis that included the previous treatment, the order of intervention and the interactions. The intake of beverages containing ß-Cx and PS brought about a significant increase in serum levels of ß-Cx, ß-sitosterol and campesterol. Intervention caused changes in almost all the markers while the order, previous treatment and the interaction did not reach statistical significance. Only the intake of the beverage containing ß-Cx plus PS brought about significant decreases in total cholesterol, c-HDL, c-LDL and bone turnover markers. CONCLUSIONS: ß-Cx improves the cholesterol-lowering effect of PS when supplied simultaneously and this combination may also be beneficial in reducing risk of osteoporosis. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov number NCT01074723.


Subject(s)
Cardiovascular Diseases/prevention & control , Cryptoxanthins/pharmacology , Phytosterols/pharmacology , Postmenopause/drug effects , Administration, Oral , Aged , Bone and Bones/drug effects , Bone and Bones/metabolism , Cholesterol/analogs & derivatives , Cholesterol/blood , Cholesterol/pharmacology , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Cross-Over Studies , Cryptoxanthins/blood , Dietary Supplements , Dose-Response Relationship, Drug , Double-Blind Method , Female , Healthy Volunteers , Humans , Hypercholesterolemia/blood , Hypercholesterolemia/drug therapy , Middle Aged , Phytosterols/blood , Postmenopause/blood , Risk Factors , Sitosterols/blood , Sitosterols/pharmacology , Treatment Outcome , Triglycerides/blood
8.
Am J Clin Nutr ; 98(2): 312-8, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23761482

ABSTRACT

BACKGROUND: Elevated plasma phytosterol concentrations are an untoward effect of parenteral nutrition (PN) with vegetable oil-based lipid emulsions (LEs). Phytosterols are elevated in neonatal cholestasis, but the relation remains controversial. OBJECTIVE: The objective was to study the effect of 5 LEs on plasma phytosterols in preterm infants. DESIGN: One hundred forty-four consecutive admitted preterm infants (birth weight: 500-1249 g) were studied. Patients were randomly assigned to receive 1 of 5 different LEs: S [100% soybean oil (SO)], MS [50% medium-chain triglycerides (MCTs) and 50% SO], MSF (50% MCTs, 40% SO, and 10% fish oil (FO)], OS (80% olive oil and 20% SO), or MOSF (30% MCTs, 25% olive oil, 30% SO, and 15% FO). Phytosterols in the LEs and in plasma (on postnatal day 7 and day 14) were measured by gas chromatography-mass spectrometry. RESULTS: Patients in the S group had significantly higher total phytosterol intakes than did the other study groups. On PN days 7 and 14, plasma phytosterol concentrations were highest in the S group and lowest in the MOSF group. Despite similar ß-sitosterol intakes between the MS and MSF groups, plasma concentrations were significantly lower in the MSF than in the MS group. Only 3 patients (2.1%) developed cholestasis: 1 in the MS, 1 in the MSF, and 1 in the MOSF group. No cases of cholestasis were observed in the S and OS groups. CONCLUSIONS: In uncomplicated preterm infants receiving routine PN, we found a correlation between phytosterol intake and plasma phytosterol concentrations; however, cholestasis was rare and no difference in liver function at 6 wk was observed.


Subject(s)
Fat Emulsions, Intravenous/administration & dosage , Infant, Premature , Parenteral Nutrition , Phytosterols/blood , Birth Weight , Cholestasis/etiology , Cholestasis/physiopathology , Emulsions/chemistry , Female , Fish Oils/administration & dosage , Gas Chromatography-Mass Spectrometry , Humans , Infant, Newborn , Infant, Premature, Diseases/therapy , Liver/drug effects , Liver/metabolism , Male , Olive Oil , Parenteral Nutrition/adverse effects , Phytosterols/administration & dosage , Plant Oils/administration & dosage , Sitosterols/administration & dosage , Sitosterols/blood , Soybean Oil/administration & dosage , Triglycerides/blood
9.
J Atheroscler Thromb ; 19(3): 237-45, 2012.
Article in English | MEDLINE | ID: mdl-22139433

ABSTRACT

AIM: Euterpe Oleracea (açai) is a fruit from the Amazon region whose chemical composition may be beneficial for individuals with atherosclerosis. We hypothesized that consumption of Euterpe Oleracea would reduce atherosclerosis development by decreasing cholesterol absorption and synthesis. METHODS: Male New Zealand rabbits were fed a cholesterol-enriched diet (0.5%) for 12 weeks, when they were randomized to receive Euterpe Oleracea extract (n = 15) or water (n = 12) plus a 0.05% cholesterol-enriched diet for an additional 12 weeks. Plasma phytosterols and desmosterol were determined by ultra-performance liquid chromatography and mass spectrometry. Atherosclerotic lesions were estimated by computerized planimetry and histomorphometry. RESULTS: At sacrifice, animals treated with Euterpe Oleracea had lower levels of total cholesterol (p =0.03), non-HDL-cholesterol (p = 0.03) and triglycerides (p = 0.02) than controls. These animals had smaller atherosclerotic plaque area in their aortas (p = 0.001) and a smaller intima/media ratio (p = 0.002) than controls, without differences in plaque composition. At the end of the study, campesterol, ß-sitosterol, and desmosterol plasma levels did not differ between groups; however, animals treated with Euterpe Oleracea showed lower desmosterol/campesterol (p = 0.026) and desmosterol/ ß-sitosterol (p =0.006) ratios than controls. CONCLUSIONS: Consumption of Euterpe Oleracea extract markedly improved the lipid profile and attenuated atherosclerosis. These effects were related in part to a better balance in the synthesis and absorption of sterols.


Subject(s)
Arecaceae/chemistry , Atherosclerosis/drug therapy , Cholesterol, Dietary/adverse effects , Lipids/analysis , Phytotherapy , Plant Extracts/therapeutic use , Animals , Atherosclerosis/etiology , Cholesterol/analogs & derivatives , Cholesterol/blood , Chromatography, High Pressure Liquid , Desmosterol/blood , Immunoenzyme Techniques , Male , Phytosterols/blood , Rabbits , Sitosterols/blood , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
10.
J Pediatr Gastroenterol Nutr ; 53(4): 440-6, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21543999

ABSTRACT

BACKGROUND AND OBJECTIVE: Plant sterols (PS) in parenteral nutrition (PN) may contribute to intestinal failure-associated liver disease. We investigated interrelations between serum PS, liver function and histology, cholesterol metabolism, and characteristics of PN. PATIENTS AND METHODS: Eleven patients with intestinal failure (mean age 6.3 years) receiving long-term PN were studied prospectively (mean 254 days) and underwent repeated measurements of serum lipids, noncholesterol sterols, including PS, and liver enzymes. PS contents of PN were analyzed. Liver biopsy was obtained in 8 patients. Twenty healthy children (mean age 5.7 years) served as controls. RESULTS: Median percentage of parenteral energy of total daily energy (PN%) was 48%, including 0.9 g · kg(-1) · day(-1) of lipids. Respective amounts of PN sitosterol, campesterol, avenasterol, and stigmasterol were 683, 71, 57, and 45 µg · kg(-1) · day(-1). Median serum concentrations of sitosterol (48 vs 7.5 µmol/L, P < 0.001), avenasterol (2.9 vs 1.9, P < 0.01), stigmasterol (1.9 vs 1.2, P < 0.005), but not that of campesterol (9.8 vs 12, P = 0.22), were increased among patients in relation to controls, and correlated with PN% (r = 0.81-0.88, P < 0.005), but not with PN fat. Serum cholesterol precursors were higher in patients than in controls. Serum liver enzymes remained close to normal range. Glutamyl transferase correlated with serum PS (r = 0.61-0.62, P < 0.05). Liver fibrosis in 5 patients reflected increased serum PS (r = 0.55-0.60, P = 0.16-0.12). CONCLUSIONS: Serum PS moderately increase during olive oil-based PN, and correlate positively with PN% and glutamyl transferase. Despite well-preserved liver function, histology often revealed significant liver damage.


Subject(s)
Cholesterol/analogs & derivatives , Intestines/pathology , Lipids/blood , Liver/pathology , Parenteral Nutrition/adverse effects , Phytosterols/blood , Sitosterols/blood , Adolescent , Biomarkers/blood , Case-Control Studies , Child , Child, Preschool , Cholestasis/pathology , Cholesterol/blood , Female , Follow-Up Studies , Humans , Infant , Lipid Metabolism/drug effects , Liver/enzymology , Liver Failure/metabolism , Male , Olive Oil , Plant Oils/administration & dosage , Prospective Studies
11.
Clin Nutr ; 30(5): 604-9, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21489663

ABSTRACT

BACKGROUND & AIMS: Phytosterols (PS) lower LDLc, but their effect on metabolic syndrome (MetS) remains unknown. We evaluated whether low-fat milk enriched with PS improves cardiovascular risk factors in these patients. METHODS: A randomised parallel trial employing 24 moderate-hypercholesterolaemic MetS patients and consisting of two 3-month intervention phases. After a 3-month healthy diet, patients were divided into two intervention groups: diet (n = 10) and diet + PS (n = 14) (2 g/day). A control group of 24 moderate-hypercholesterolaemic patients without MetS (matched in age and BMI) underwent the same procedure. RESULTS: Neither dietary intervention nor enrichment of PS induced any improvement in the serum lipoprotein profile of MetS patients. By contrast, in the non-MetS population, a healthy diet effectively reduced TC, LDLc, non-HDLc and Apo B-100, with further decreases in TC (6.9%), LDLc (10.5%), non-HDLc (10.3%), Apo B-100 (6.2%) and Apo B-100/ApoA-I ratio (11.6%) being observed when PS were administered. No differences in LDL diameter, hsCRP or homocysteine were detected in any of the groups after consuming PS. This supplementation produced a significant increase in PS levels only in the non-MetS population. CONCLUSIONS: PS therapy appears to be of little value to MetS patients, likely due to its reduced intestinal cholesterol absorption. The efficacy of PS as hypocholesterolaemic agents is thus limited.


Subject(s)
Dietary Supplements , Hypercholesterolemia/diet therapy , Hypolipidemic Agents/therapeutic use , Intestinal Absorption , Metabolic Syndrome/blood , Metabolic Syndrome/diet therapy , Phytosterols/therapeutic use , Adult , Anticholesteremic Agents/blood , Anticholesteremic Agents/metabolism , Anticholesteremic Agents/therapeutic use , Cardiovascular Diseases/epidemiology , Cholesterol/analogs & derivatives , Cholesterol/blood , Cholesterol/metabolism , Cholesterol/therapeutic use , Cholesterol, Dietary/metabolism , Female , Humans , Hypercholesterolemia/etiology , Hypercholesterolemia/metabolism , Hypercholesterolemia/physiopathology , Hypolipidemic Agents/blood , Hypolipidemic Agents/metabolism , Lipoproteins/blood , Male , Metabolic Syndrome/metabolism , Metabolic Syndrome/physiopathology , Middle Aged , Phytosterols/blood , Phytosterols/metabolism , Risk Factors , Severity of Illness Index , Sitosterols/blood , Sitosterols/metabolism , Sitosterols/therapeutic use , Spain/epidemiology
12.
Eur J Nutr ; 49(2): 111-7, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19774436

ABSTRACT

BACKGROUND: Today, consumers meet abundant supply of functional foods with plant stanol increments for serum cholesterol lowering purposes. However, efficacy and safety of plant stanols intake beyond 4 g/day have remained unexplored. AIM OF THE STUDY: We evaluated the effects of very high daily intake of plant stanols (8.8 g/day) as esters on cholesterol metabolism, and serum levels of plant sterols and stanols. METHODS: In a randomized, double-blind, parallel study of 49 hypercholesterolemic subjects (mean age 62 years, range 41-73) consumed a test diet without (control, n = 24), and with added plant stanol esters (staest, n = 25) over 10 weeks followed by 4 weeks on home diet. Serum lipids, lipoprotein lipids, and non-cholesterol sterols were determined at baseline, during intervention, and 4 weeks afterwards. Cholesterol precursor sterol lathosterol reflected cholesterol synthesis, and serum plant sterols and cholestanol mirrored cholesterol absorption. RESULTS: When compared with controls, 8.8 g/day of plant stanols reduced serum and LDL cholesterol by 12 and 17% (P < 0.01 for both). Synthesis marker lathosterol was increased by 30%, while absorption markers decreased up to 62% when compared with controls (P < 0.001 for both). Serum plant stanols increased slightly, but significantly compared with controls (serum sitostanol during intervention, controls: 16 +/- 1 microg/dL, staest: 37 +/- 2 microg/dL, serum campestanol during intervention, controls: 0.5 +/- 0 microg/dL, staest: 9 +/- 1 microg/dL, P < 0.001 for both). Changes in serum cholesterol, non-cholesterol sterols, and plant stanols were normalized during post-treatment weeks. CONCLUSIONS: Serum plant stanol levels remained at comparable low levels as in studies with daily intake of 2-3 g, and were normalized in 4 weeks suggesting that daily intake of 8.8 g of plant stanols might not increase systemic availability of plant stanols, but reduces effectively serum cholesterol and plant sterol levels.


Subject(s)
Anticholesteremic Agents/blood , Anticholesteremic Agents/therapeutic use , Hypercholesterolemia/drug therapy , Phytosterols/blood , Phytotherapy , Sitosterols/blood , Sitosterols/therapeutic use , Adult , Aged , Anticholesteremic Agents/administration & dosage , Biomarkers/blood , Cholesterol/blood , Cholesterol/metabolism , Double-Blind Method , Esters/therapeutic use , Female , Follow-Up Studies , Food, Formulated , Humans , Intestinal Absorption , Lipids/blood , Lipoproteins/blood , Male , Middle Aged , Sitosterols/administration & dosage , Time Factors
13.
Clin Nutr ; 29(1): 112-8, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19709787

ABSTRACT

BACKGROUND & AIMS: Intake of 2-3 g/d of plant stanols as esters lowers LDL cholesterol level, but there is no information about the efficacy and safety of a respective very high daily intake. We studied the effects of 8.8 g/d of plant stanols as esters on serum lipids and safety variables in subjects with mild to moderate hypercholesterolemia. METHODS: In a randomized, double-blind, placebo-controlled study the intervention (n=25) and control (n=24) groups consumed spread and drink enriched or not with plant stanol esters for 10 weeks. RESULTS: Plant stanols reduced serum total and LDL cholesterol concentrations by 12.8 and 17.3% from baseline and by 12.0 and 17.1% from controls (P<0.01 for all). Liver enzymes, markers of hemolysis, and blood cells were unchanged. Serum vitamins A, D, and gamma-tocopherol concentrations, and the ratios of alpha-tocopherol to cholesterol were unchanged. Serum beta-carotene concentrations decreased significantly from baseline and were different from controls even when adjusted for cholesterol. Serum alpha-carotene concentration and alpha-carotene/cholesterol ratio were not different from controls. CONCLUSIONS: High intake of plant stanols reduced LDL cholesterol values without any other side effects than reduction of serum beta-carotene concentration. However, the end product, serum vitamin A levels, were unchanged. The results suggest that plant stanol ester intake can be increased to induce a greater cholesterol lowering effect.


Subject(s)
Carotenoids/blood , Diet/methods , Hypolipidemic Agents/blood , Lipids/blood , Sitosterols/blood , Vitamins/blood , Adolescent , Adult , Aged , Biomarkers/blood , Cholesterol/blood , Diet/statistics & numerical data , Double-Blind Method , Female , Finland , Humans , Hypercholesterolemia/blood , Hypercholesterolemia/diet therapy , Hypolipidemic Agents/administration & dosage , Hypolipidemic Agents/pharmacology , Male , Middle Aged , Sitosterols/administration & dosage , Sitosterols/pharmacology , Vitamin A/blood , Vitamin D/blood , Young Adult , alpha-Tocopherol/blood , beta Carotene/blood
14.
Br J Nutr ; 102(12): 1740-51, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19772679

ABSTRACT

Rapeseed oil (RSO) is a novel source of plant sterols, containing the unique brassicasterol in concentrations higher than allowed for plant sterol blends in food products in the European Union. Effects of RSO sterols and stanols on aortic atherosclerosis were studied in cholesterol-fed heterozygous Watanabe heritable hyperlipidaemic (Hh-WHHL) rabbits. Four groups (n 18 per group) received a cholesterol-added (2 g/kg) standard chow or this diet with added RSO stanol esters (17 g/kg), RSO stanol esters (34 g/kg) or RSO sterol esters (34 g/kg) for 18 weeks. Feeding RSO stanol esters increased plasma campestanol (P < 0.001) and sitostanol (P < 0.001) and aortic campestanol (P < 0.05) compared with controls. Feeding RSO sterol esters increased concentrations of plasma campesterol (P < 0.001), sitosterol (P < 0.001) and brassicasterol (P < 0.001) and aortic campesterol (P < 0.01). Significantly lower plasma cholesterol (P < 0.001) was recorded in the treated groups after 3 weeks and throughout the study. LDL-cholesterol was reduced 50 % in the high-dose RSO sterol ester (P < 0.01) and high-dose RSO stanol ester (P < 0.001) groups compared with controls. Atherosclerotic lesions were found in three rabbits in each of the RSO stanol ester groups and in one in the RSO sterol ester group. Aortic cholesterol was decreased in the treated groups (P < 0.001) in response to lowering of plasma cholesterol induced by RSO sterol and stanol esters. In conclusion, RSO stanol and sterol esters with a high concentration of brassicasterol were well tolerated. They were hypocholesterolaemic and inhibited experimental atherosclerosis in cholesterol-fed Hh-WHHL rabbits. A significant uptake of plant sterols into the blood and incorporation of campesterol and campestanol into aortic tissue was recorded.


Subject(s)
Atherosclerosis/prevention & control , Cholesterol, Dietary/administration & dosage , Hyperlipidemias/diet therapy , Phytosterols/administration & dosage , Plant Oils/chemistry , Animals , Aorta/chemistry , Atherosclerosis/metabolism , Atherosclerosis/pathology , Cholestadienols/administration & dosage , Cholesterol/analogs & derivatives , Cholesterol/analysis , Cholesterol/blood , Fatty Acids, Monounsaturated , Female , Heterozygote , Hyperlipidemias/genetics , Lipids/blood , Male , Phytosterols/analysis , Phytosterols/blood , Plant Oils/administration & dosage , Rabbits , Rapeseed Oil , Sitosterols/blood
15.
Zhonghua Yu Fang Yi Xue Za Zhi ; 43(12): 1060-3, 2009 Dec.
Article in Chinese | MEDLINE | ID: mdl-20193499

ABSTRACT

OBJECTIVE: To investigate the dietary phytosterol intake of elderly women in three different cities of China, and to compare the main dietary sources, so that to discuss the relationship of dietary phytosterol intake and serum lipids. METHODS: Based on the dietary pattern, women more than 50 years old from Beijing, Hefei and Urumchi were chosen as testers, 80 - 100 people for each city respectively. The dietary survey was done by continues 24 hours review of two days, the plant food were collected and the phytosterol content (include beta-sitosterol, campesterol, stigmasterol, sitostanol) were analyzed by GC methods, the total phytosterols content were calculated. The dietary phytosterol intake were calculated and serum lipids were also analyzed in all the testers. RESULTS: Testers from Beijing, Hefei and Urumchi were 100, 101 and 84 respectively. The average dietary phytosterol intake of people in Beijing and Hefei were 340.3 mg/d and 313.5 mg/d, the main sources were plant oil and cereals, while the average dietary phytosterol intake of people in Urumchi were 550.4 mg/d, higher than the other two cities (t values were 9.369, 10.420, respectively, both P values < 0.01), the main source in Urumchi was cereal (provide 53.1% of the total phytosterol intake). The laboratory results showed, testers in Urumchi had significantly lower serum TC content ((4.04 +/- 0.78) mmol/L) than that in Beijing ((4.89 +/- 0.91) mmol/L) and Hefei ((4.71 +/- 0.83) mmol/L) (t value were 6.766 and 5.401 respectively, both P values < 0.01); serum TG content in Urumchi((1.01 +/- 0.48) mmol/L) was also lower than that in Beijing ((1.31 +/- 0.53) mmol/L) and Hefei ((1.66 +/- 0.75) mmol/L) (t values were 3.343 and 7.293 respectively, both P values < 0.01); the serum glucose is also lower in testers in Urumchi ((5.02 +/- 2.18) mmol/L) compared with testers in Beijing ((5.69 +/- 1.53) mmol/L, t = 2.561, P < 0.05) and Hefei ((5.78 +/- 1.53) mmol/L, t = 2.934, P < 0.01). CONCLUSION: Different dietary pattern result in significantly different dietary phytosterol intake in elder women in three cities, higher, phytosterol intake seemed to contribute to lower serum lipids.


Subject(s)
Cholesterol, Dietary/metabolism , Lipids/blood , Phytosterols/metabolism , Aged , Aged, 80 and over , China , Cholesterol/analogs & derivatives , Cholesterol/blood , Female , Humans , Middle Aged , Phytosterols/blood , Sitosterols/blood , Urban Population
16.
Eur J Clin Nutr ; 63(5): 684-91, 2009 May.
Article in English | MEDLINE | ID: mdl-18270526

ABSTRACT

BACKGROUND/OBJECTIVES: To assess safety during a diet based on low-fat foods enriched with nonesterified wood-derived plant sterols and mineral nutrients related to serum phytosterol, sex hormone and fat-soluble vitamin metabolism. SUBJECTS/METHODS: Seventy-one study participants (52 women, 19 men) with mild-to-moderate hypercholesterolemia completed the double-blind, placebo-controlled feeding trial lasting for 15 weeks. The subjects were randomly allocated to the sterol group receiving food items enriched with mineral nutrients as well as with a total of 1.25, 2.5 and 5.0 g per day of plant sterols during the first, second and third 5-week periods, respectively, or to the placebo group receiving similar food items without plant sterols. This outpatient clinical trial with free-living subjects was carried out at two hospital clinics. RESULTS: Two significant findings were observed. Serum sitosterol concentrations increased from 2.84 to 5.35 mg l(-1) (P<0.004 vs placebo) but those of serum total plant sterols did not because of compensatory changes in other phytosterols. The highest plant sterol levels did not exceed 0.6% of total serum sterols. Serum alpha-tocopherol concentrations decreased in the sterol group by 10% (P<0.0002), but the between-group difference disappeared after adjusting for the change in the carrier (LDL cholesterol). CONCLUSIONS: Fifteen-week consumption of natural nonesterified plant sterol-enriched food does not cause any serious adverse effects during such a period. However, serum alpha-tocopherol levels were somewhat reduced in the sterol group suggesting that long-term effects of plant sterols on serum fat-soluble vitamin concentrations should be further explored, especially in relation to very low-fat diets.


Subject(s)
Food, Fortified , Hypolipidemic Agents/blood , Phytosterols/adverse effects , Sitosterols/blood , Adult , Aged , Cholesterol, LDL/blood , Diet , Double-Blind Method , Female , Finland , Gonadal Steroid Hormones/blood , Humans , Hypercholesterolemia/drug therapy , Male , Middle Aged , Phytosterols/blood , Phytosterols/therapeutic use , Vitamins/blood , alpha-Tocopherol/blood
17.
Dtsch Med Wochenschr ; 133(22): 1201-4, 2008 May.
Article in German | MEDLINE | ID: mdl-18491276

ABSTRACT

"Functional foods" supplemented with plant sterols are advertised and added to regular meals to reduce serum cholesterol concentrations. The effects of increased phytosterol levels on cardiovascular diseases, however, are not known. Findings in patients with sitosterolemia, data from epidemiological studies, and experimental data from animal studies suggest that plant sterols may potentially exert negative cardiovascular effects. Additional studies investigating relevant clinical endpoints are needed before a diet supplemented with plant sterols can be recommended in the prevention of cardiovascular diseases.


Subject(s)
Cardiovascular Diseases/prevention & control , Dietary Supplements , Phytosterols/administration & dosage , Animals , Anticholesteremic Agents/administration & dosage , Anticholesteremic Agents/adverse effects , Cardiovascular Diseases/etiology , Cholesterol/blood , Humans , Phytosterols/adverse effects , Risk Factors , Sitosterols/blood
18.
Am J Clin Nutr ; 86(3): 790-6, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17823447

ABSTRACT

BACKGROUND: Plant sterol (PS)-enriched foods have been shown to reduce plasma LDL-cholesterol concentrations. In most studies, however, PSs were incorporated into food products of high fat content. OBJECTIVE: We examined the effect of daily consumption of PS-supplemented low-fat fermented milk (FM) on the plasma lipid profile and on systemic oxidative stress in hypercholesterolemic subjects. DESIGN: Hypercholesterolemic subjects (LDL-cholesterol concentrations >or=130 and

Subject(s)
Hypercholesterolemia/drug therapy , Lipids/blood , Milk/chemistry , Oxidative Stress/drug effects , Phytosterols/pharmacology , Animals , C-Reactive Protein/metabolism , Carotenoids/blood , Cholesterol/analogs & derivatives , Cholesterol/blood , Cholesterol/pharmacology , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Double-Blind Method , Female , Fermentation , Humans , Hypercholesterolemia/blood , Male , Middle Aged , Patient Compliance , Phytosterols/blood , Sitosterols/blood , Sitosterols/pharmacology , Treatment Outcome , Triglycerides/blood
19.
Br J Nutr ; 98(5): 890-9, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17537294

ABSTRACT

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.


Subject(s)
Brain/metabolism , Phytosterols/pharmacokinetics , Plant Oils/chemistry , Sitosterols/pharmacokinetics , Animal Feed/analysis , Animal Nutritional Physiological Phenomena , Animals , Blood-Brain Barrier , Cholesterol/metabolism , Disease Models, Animal , Fatty Acids, Monounsaturated , Female , Heterozygote , Homozygote , Hyperlipoproteinemia Type II/metabolism , Liver/metabolism , Male , Phytosterols/blood , Rabbits , Rapeseed Oil , Sitosterols/blood
20.
Clin Pharmacol Ther ; 78(1): 60-8, 2005 Jul.
Article in English | MEDLINE | ID: mdl-16003294

ABSTRACT

BACKGROUND: Myopathy, probably caused by 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibition in skeletal muscle, rarely occurs in patients taking statins. This study was designed to assess the effect of high-dose statin treatment on cholesterol and ubiquinone metabolism and mitochondrial function in human skeletal muscle. METHODS: Forty-eight patients with hypercholesterolemia (33 men and 15 women) were randomly assigned to receive 80 mg/d of simvastatin (n = 16), 40 mg/d of atorvastatin (n = 16), or placebo (n = 16) for 8 weeks. Plasma samples and muscle biopsy specimens were obtained at baseline and at the end of the follow-up. RESULTS: The ratio of plasma lathosterol to cholesterol, a marker of endogenous cholesterol synthesis, decreased significantly by 66% in both statin groups. Muscle campesterol concentrations increased from 21.1 +/- 7.1 nmol/g to 41.2 +/- 27.0 nmol/g in the simvastatin group and from 22.6 +/- 8.6 nmol/g to 40.0 +/- 18.7 nmol/g in the atorvastatin group (P = .005, repeated-measurements ANOVA). The muscle ubiquinone concentration was reduced significantly from 39.7 +/- 13.6 nmol/g to 26.4 +/- 7.9 nmol/g (P = .031, repeated-measurements ANOVA) in the simvastatin group, but no reduction was observed in the atorvastatin or placebo group. Respiratory chain enzyme activities were assessed in 6 patients taking simvastatin with markedly reduced muscle ubiquinone and in matched subjects selected from the atorvastatin (n = 6) and placebo (n = 6) groups. Respiratory chain enzyme and citrate synthase activities were reduced in the patients taking simvastatin. CONCLUSIONS: High-dose statin treatment leads to changes in the skeletal muscle sterol metabolism. Furthermore, aggressive statin treatment may affect mitochondrial volume.


Subject(s)
Cholesterol/analogs & derivatives , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Muscles/drug effects , Muscles/metabolism , Adult , Age Factors , Aged , Atorvastatin , Biopsy , Cholesterol/biosynthesis , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, HDL/drug effects , Cholesterol, LDL/blood , Cholesterol, LDL/drug effects , Citrate (si)-Synthase/drug effects , Citrate (si)-Synthase/metabolism , Dose-Response Relationship, Drug , Double-Blind Method , Electron Transport/drug effects , Female , Heptanoic Acids/blood , Heptanoic Acids/pharmacology , Heptanoic Acids/therapeutic use , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hypercholesterolemia/drug therapy , Male , Middle Aged , Muscles/pathology , Patient Selection , Phytosterols/biosynthesis , Phytosterols/blood , Pyrroles/blood , Pyrroles/pharmacology , Pyrroles/therapeutic use , Sex Factors , Simvastatin/blood , Simvastatin/pharmacology , Simvastatin/therapeutic use , Sitosterols/blood , Succinate Cytochrome c Oxidoreductase/drug effects , Succinate Cytochrome c Oxidoreductase/metabolism , Time Factors , Ubiquinone/blood , Ubiquinone/chemistry
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