The Experts below are selected from a list of 17709 Experts worldwide ranked by ideXlab platform
Richard E Ostlund - One of the best experts on this subject based on the ideXlab platform.
-
Natural Dietary Phytosterols.
Journal of AOAC International, 2015Co-Authors: Susan B. Racette, Lina Ma, Richard E OstlundAbstract:Abstract 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.
-
Plasma Biomarker of Dietary Phytosterol Intake
PLOS ONE, 2015Co-Authors: Susan B. Racette, Michael Wallendorf, Catherine Anderson Spearie, Lina Ma, Richard E OstlundAbstract:Background Dietary 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.
-
Plasma biomarker of dietary Phytosterol intake
PLoS ONE, 2015Co-Authors: Xin Lin, Michael Wallendorf, Catherine Anderson Spearie, Susan B. Racette, L. Ma, Richard E OstlundAbstract:BACKGROUND: Dietary 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.\n\nMETHODS AND FINDINGS: Data 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).\n\nCONCLUSION: The 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.
-
Phytosterol deficient and high Phytosterol diets developed for controlled feeding studies
Journal of The American Dietetic Association, 2009Co-Authors: Susan B. Racette, Catherine Anderson Spearie, Katherine M Phillips, Richard E OstlundAbstract:Abstract Phytosterols reduce cholesterol absorption and low-density lipoprotein cholesterol concentrations, but the quantity and physiological significance of Phytosterols in common diets are generally unknown because nutrient databases do not contain comprehensive Phytosterol data. The primary aim of this study was to design prototype Phytosterol-deficient and high-Phytosterol diets for use in controlled feeding studies of the influence of Phytosterols on health. A second aim was to quantify the Phytosterol content of these prototype diets and three other diets consumed in the United States. This study was conducted from June 2001 to September 2008 and involved designing, preparing, and then analyzing five different diets: an experimental Phytosterol-deficient control diet, a relatively high-Phytosterol diet based on the Dietary Approaches to Stop Hypertension diet, American Heart Association diet, Atkins lifetime maintenance plan, and a vegan diet. A single day of meals for each diet was homogenized and the resulting composites were analyzed for free, esterified, and glycosylated Phytosterols by gas chromatography. Independent samples t tests were used to compare the diets' total Phytosterol content. The total Phytosterol content of the experimental Phytosterol-deficient diet was 64 mg/2,000 kcal, with progressively larger quantities in Atkins, American Heart Association, vegan, and the high-Phytosterol Dietary Approaches to Stop Hypertension diet (163, 340, 445, and 500 mg/2,000 kcal, respectively). Glycosylated Phytosterols, which are often excluded from Phytosterol analyses, comprised 15.9%±5.9% of total Phytosterols. In summary, Phytosterol-deficient and high-Phytosterol diets that conform to recommended macronutrient guidelines and are palatable can now be used in controlled feeding studies.
-
Phytosterol glycosides reduce cholesterol absorption in humans
AJP: Gastrointestinal and Liver Physiology, 2009Co-Authors: Xin Lin, C. L. Anderson Spearie, Susan B. Racette, L. Ma, Richard E OstlundAbstract:Dietary Phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that Phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series of three single-meal tests given at intervals of 2 wk to each of 11 healthy subjects. In a randomized crossover design, participants received approximately 300 mg of added Phytosterols in the form of Phytosterol glycosides or Phytosterol esters, or placebo in a test breakfast also containing 30 mg cholesterol-d7. Cholesterol absorption was estimated by mass spectrometry of plasma cholesterol-d7 enrichment 4-5 days after each test. Compared with the placebo test, Phytosterol glycosides reduced cholesterol absorption by 37.6+/-4.8% (P
Susan B. Racette - One of the best experts on this subject based on the ideXlab platform.
-
Natural Dietary Phytosterols.
Journal of AOAC International, 2015Co-Authors: Susan B. Racette, Lina Ma, Richard E OstlundAbstract:Abstract 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.
-
Plasma Biomarker of Dietary Phytosterol Intake
PLOS ONE, 2015Co-Authors: Susan B. Racette, Michael Wallendorf, Catherine Anderson Spearie, Lina Ma, Richard E OstlundAbstract:Background Dietary 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.
-
Plasma biomarker of dietary Phytosterol intake
PLoS ONE, 2015Co-Authors: Xin Lin, Michael Wallendorf, Catherine Anderson Spearie, Susan B. Racette, L. Ma, Richard E OstlundAbstract:BACKGROUND: Dietary 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.\n\nMETHODS AND FINDINGS: Data 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).\n\nCONCLUSION: The 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.
-
Phytosterol deficient and high Phytosterol diets developed for controlled feeding studies
Journal of The American Dietetic Association, 2009Co-Authors: Susan B. Racette, Catherine Anderson Spearie, Katherine M Phillips, Richard E OstlundAbstract:Abstract Phytosterols reduce cholesterol absorption and low-density lipoprotein cholesterol concentrations, but the quantity and physiological significance of Phytosterols in common diets are generally unknown because nutrient databases do not contain comprehensive Phytosterol data. The primary aim of this study was to design prototype Phytosterol-deficient and high-Phytosterol diets for use in controlled feeding studies of the influence of Phytosterols on health. A second aim was to quantify the Phytosterol content of these prototype diets and three other diets consumed in the United States. This study was conducted from June 2001 to September 2008 and involved designing, preparing, and then analyzing five different diets: an experimental Phytosterol-deficient control diet, a relatively high-Phytosterol diet based on the Dietary Approaches to Stop Hypertension diet, American Heart Association diet, Atkins lifetime maintenance plan, and a vegan diet. A single day of meals for each diet was homogenized and the resulting composites were analyzed for free, esterified, and glycosylated Phytosterols by gas chromatography. Independent samples t tests were used to compare the diets' total Phytosterol content. The total Phytosterol content of the experimental Phytosterol-deficient diet was 64 mg/2,000 kcal, with progressively larger quantities in Atkins, American Heart Association, vegan, and the high-Phytosterol Dietary Approaches to Stop Hypertension diet (163, 340, 445, and 500 mg/2,000 kcal, respectively). Glycosylated Phytosterols, which are often excluded from Phytosterol analyses, comprised 15.9%±5.9% of total Phytosterols. In summary, Phytosterol-deficient and high-Phytosterol diets that conform to recommended macronutrient guidelines and are palatable can now be used in controlled feeding studies.
-
Phytosterol glycosides reduce cholesterol absorption in humans
AJP: Gastrointestinal and Liver Physiology, 2009Co-Authors: Xin Lin, C. L. Anderson Spearie, Susan B. Racette, L. Ma, Richard E OstlundAbstract:Dietary Phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that Phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series of three single-meal tests given at intervals of 2 wk to each of 11 healthy subjects. In a randomized crossover design, participants received approximately 300 mg of added Phytosterols in the form of Phytosterol glycosides or Phytosterol esters, or placebo in a test breakfast also containing 30 mg cholesterol-d7. Cholesterol absorption was estimated by mass spectrometry of plasma cholesterol-d7 enrichment 4-5 days after each test. Compared with the placebo test, Phytosterol glycosides reduced cholesterol absorption by 37.6+/-4.8% (P
William F. Stenson - One of the best experts on this subject based on the ideXlab platform.
-
inhibition of cholesterol absorption by Phytosterol replete wheat germ compared with Phytosterol depleted wheat germ
The American Journal of Clinical Nutrition, 2003Co-Authors: Richard E Ostlund, Susan B. Racette, William F. StensonAbstract:Background: Low-fat vegetable foods contain Phytosterols, but it is not known whether they are in biologically active forms or whether their concentrations are high enough to reduce cholesterol absorption and favorably affect lipid metabolism. Objective: The objective was to establish whether the selective removal of Phytosterols from wheat germ would increase the cholesterol absorption measured from test meals composed of wheat germ muffins. Design: Wheat germ, which has a high content of Phytosterols relative to total fat, was chosen as a low-fat test food. Cholesterol absorption was measured 3 times in 10 subjects. Each test meal was a muffin containing 30 mg heptadeuterated cholesterol tracer and, in random order, 80 g original wheat germ containing 328 mg Phytosterols, wheat germ from which Phytosterols had been selectively extracted, or extracted wheat germ reconstituted with purified Phytosterols. Changes in cholesterol absorption were monitored by the measurement of tracer enrichment of plasma cholesterol 4 and 5 d after each meal with the use of negative ion mass spectrometry. Results: Tracer enrichment of plasma cholesterol was 42.8% higher after consumption of Phytosterol-free wheat germ than after that of the original wheat germ (0.415 ± 0.035 compared with 0.291 ± 0.024 � mol tracer/mmol cholesterol; P < 0.01). Tracer enrichment of plasma cholesterol was not significantly different between the wheat germ with extracted-and-reconstituted Phytosterol (0.305 ± 0.022 � mol tracer/mmol cholesterol) and the original wheat germ. Conclusion: The efficiency of cholesterol absorption from test meals was substantially lower after consumption of original wheat germ than after consumption of Phytosterol-free wheat germ, which suggests that endogenous Phytosterols in wheat germ and possibly in other low-fat vegetable foods may have important effects on cholesterol absorption and metabolism that are independent of major nutrients. Am J Clin Nutr 2003;77:1385‐9.
-
Inhibition of cholesterol absorption by Phytosterol-replete wheat germ compared with Phytosterol-depleted wheat germ
American Journal of Clinical Nutrition, 2003Co-Authors: Richard E Ostlund, Susan B. Racette, William F. StensonAbstract:BACKGROUND: Low-fat vegetable foods contain Phytosterols, but it is not known whether they are in biologically active forms or whether their concentrations are high enough to reduce cholesterol absorption and favorably affect lipid metabolism. OBJECTIVE: The objective was to establish whether the selective removal of Phytosterols from wheat germ would increase the cholesterol absorption measured from test meals composed of wheat germ muffins. DESIGN: Wheat germ, which has a high content of Phytosterols relative to total fat, was chosen as a low-fat test food. Cholesterol absorption was measured 3 times in 10 subjects. Each test meal was a muffin containing 30 mg heptadeuterated cholesterol tracer and, in random order, 80 g original wheat germ containing 328 mg Phytosterols, wheat germ from which Phytosterols had been selectively extracted, or extracted wheat germ reconstituted with purified Phytosterols. Changes in cholesterol absorption were monitored by the measurement of tracer enrichment of plasma cholesterol 4 and 5 d after each meal with the use of negative ion mass spectrometry. RESULTS: Tracer enrichment of plasma cholesterol was 42.8% higher after consumption of Phytosterol-free wheat germ than after that of the original wheat germ (0.415 +/- 0.035 compared with 0.291 +/- 0.024 micro mol tracer/mmol cholesterol; P < 0.01). Tracer enrichment of plasma cholesterol was not significantly different between the wheat germ with extracted-and-reconstituted Phytosterol (0.305 +/- 0.022 micro mol tracer/mmol cholesterol) and the original wheat germ. CONCLUSION: The efficiency of cholesterol absorption from test meals was substantially lower after consumption of original wheat germ than after consumption of Phytosterol-free wheat germ, which suggests that endogenous Phytosterols in wheat germ and possibly in other low-fat vegetable foods may have important effects on cholesterol absorption and metabolism that are independent of major nutrients.
-
Effects of trace components of dietary fat on cholesterol metabolism: Phytosterols, oxysterols, and squalene
Nutrition Reviews, 2002Co-Authors: Richard E Ostlund, Susan B. Racette, William F. StensonAbstract:The effect of dietary fats on serum cholesterol is widely assumed to be due solely to the fatty acids and cholesterol they contain. Phytosterols, sterol oxidation products, and sterol precursors such as squalene, however, are often present in dietary fats. Little is known of the physiology of these substances in natural foods and most published diet studies do not consider them at all. Supplementation of the diet with high-dose Phytosterols is now recommended for prevention of heart disease, but both recent and old data strongly suggest that the lower levels of Phytosterols naturally present in vegetable fats may also reduce cholesterol absorption and serum cholesterol substantially. Moreover, unmeasured Phytosterols may confound otherwise well-controlled diet studies because there is an inverse correlation between Phytosterol and saturated fatty acid content of vegetable fats. Sterol oxidation products, many of which are found in foods, are potent regulators of lipoprotein and cholesterol transport pathways in vitro. Squalene is a Phytosterol precursor abundant in olive oil that is at least partly absorbed and then quantitatively converted to cholesterol. The effects of dietary triglyceride-derived fatty acids have not been experimentally separated from the effects of trace fat components in most clinical studies. A better understanding of the activity of sterol-related dietary components is needed to reduce variability in diet studies, accurately assess the effects of dietary fatty acids and to maximize the effectiveness of dietary treatment for hypercholesterolemia.
P. A. Hepburn - One of the best experts on this subject based on the ideXlab platform.
-
Safety evaluation of Phytosterol esters. Part 8. Lack of genotoxicity and subchronic toxicity with Phytosterol oxides.
Food and Chemical Toxicology, 2004Co-Authors: P. A. Hepburn, A. M. Wolfreys, Paul BaldrickAbstract:Vegetable oil spreads containing Phytosterol-esters are marketed as a cholesterol-lowering functional food in more than 20 countries worldwide. An extensive package of safety data has shown Phytosterol-esters to be safe for human use. However, even though Phytosterols are very stable molecules, oxidation may occur at low levels under extreme heating conditions, resulting in Phytosterol oxides. As there is some suggestion of adverse biological effects in the literature for the related cholesterol oxidation products, safety data have been generated for Phytosterol oxides. A Phytosterol oxide concentrate (POC) was generated by prolonged heating of Phytosterol-esters in the presence of oxygen. The genotoxicity and subchronic toxicity of this mixture was assessed in a series of in vitro genotoxicity assays (bacterial mutation, chromosome aberration and micronucleus) and a subchronic feeding study in the rat. Results showed that a Phytosterol oxide concentrate containing approximately 30% Phytosterol oxides did not possess genotoxic potential and no obvious evidence of toxicity when administered in the diet of the rat for 90 consecutive days. In the latter study, a NOEL was established at an estimated dietary level of Phytosterol oxides of 128 mg/kg/day for males and 144 mg/kg/day for females. In conclusion, these materials have been shown to raise no obvious concerns for human safety.
-
Safety evaluation of Phytosterol esters. Part 8. Lack of genotoxicity and subchronic toxicity with Phytosterol oxides
Food and Chemical Toxicology, 2004Co-Authors: L J Lea, P. A. Hepburn, A. M. Wolfreys, Paul BaldrickAbstract:Vegetable oil spreads containing Phytosterol-esters are marketed as a cholesterol-lowering functional food in more than 20 countries worldwide. An extensive package of safety data has shown Phytosterol-esters to be safe for human use. However, even though Phytosterols are very stable molecules, oxidation may occur at low levels under extreme heating conditions, resulting in Phytosterol oxides. As there is some suggestion of adverse biological effects in the literature for the related cholesterol oxidation products, safety data have been generated for Phytosterol oxides. A Phytosterol oxide concentrate (POC) was generated by prolonged heating of Phytosterol-esters in the presence of oxygen. The genotoxicity and subchronic toxicity of this mixture was assessed in a series of in vitro genotoxicity assays (bacterial mutation, chromosome aberration and micronucleus) and a subchronic feeding study in the rat. Results showed that a Phytosterol oxide concentrate containing approximately 30% Phytosterol oxides did not possess genotoxic potential and no obvious evidence of toxicity when administered in the diet of the rat for 90 consecutive days. In the latter study, a NOEL was established at an estimated dietary level of Phytosterol oxides of 128 mg/kg/day for males and 144 mg/kg/day for females. In conclusion, these materials have been shown to raise no obvious concerns for human safety. © 2004 Elsevier Ltd. All rights reserved.
-
Safety evaluation of Phytosterol esters. Part 7. Assessment of mutagenic activity of Phytosterols, Phytosterol esters and the cholesterol derivative, 4-cholesten-3-one
Food and Chemical Toxicology, 2002Co-Authors: A. M. Wolfreys, P. A. HepburnAbstract:Abstract Phytosterol esters are Phytosterols derived from vegetable oils following esterification to fatty acids. When Phytosterols are added to foods, they inhibit the absorption of dietary and endogenous cholesterol and thereby reduce blood cholesterol concentrations. As part of a comprehensive programme of safety assessment, the mutagenic potential of Phytosterols and Phytosterol esters has been assessed in a bacterial mutation assay and an in vitro chromosome aberration assay. In addition, an in vitro mammalian cell gene mutation assay and two in vivo mutagenicity studies, namely rat bone marrow micronucleus and liver unscheduled DNA synthesis (UDS) assays, were conducted on Phytosterol esters only. Phytosterols and Phytosterol esters did not show any evidence of mutagenic activity in any of these assays. A breakdown product of cholesterol is 4-cholesten-3-one and thus the amount of 4-cholesten-3-one in the gut may increase following supplementation of foods with Phytosterol-esters. 4-cholesten-3-one had been previously reported as mutagenic but, due to various shortcomings, these data could not be used to assess the mutagenic activity of 4-cholesten-3-one. The mutagenic activity of 4-cholesten-3-one and its major faecal by-products, 5β-cholestan-3-one, was assessed in two in vitro assays, a bacterial mutation assay and an in vitro chromosome aberration assay. Neither 4-cholesten-3-one nor 5β-cholestan-3-one showed evidence of mutagenic activity in these assays.
-
Safety evaluation of Phytosterol esters. Part 7. Assessment of mutagenic activity of Phytosterols, Phytosterol esters and the cholesterol derivative, 4-cholesten-3-one
Food and Chemical Toxicology, 2002Co-Authors: A. M. Wolfreys, P. A. HepburnAbstract:Phytosterol esters are Phytosterols derived from vegetable oils following esterification to fatty acids. When Phytosterols are added to foods, they inhibit the absorption of dietary and endogenous cholesterol and thereby reduce blood cholesterol concentrations. As part of a comprehensive programme of safety assessment, the mutagenic potential of Phytosterols and Phytosterol esters has been assessed in a bacterial mutation assay and an in vitro chromosome aberration assay. In addition, an in vitro mammalian cell gene mutation assay and two in vivo mutagenicity studies, namely rat bone marrow micronucleus and liver unscheduled DNA synthesis (UDS) assays, were conducted on Phytosterol esters only. Phytosterols and Phytosterol esters did not show any evidence of mutagenic activity in any of these assays. A breakdown product of cholesterol is 4-cholesten-3-one and thus the amount of 4-cholesten-3-one in the gut may increase following supplementation of foods with Phytosterol-esters. 4-cholesten-3-one had been previously reported as mutagenic but, due to various shortcomings, these data could not be used to assess the mutagenic activity of 4-cholesten-3-one. The mutagenic activity of 4-cholesten-3-one and its major faecal by-products, 5??-cholestan-3-one, was assessed in two in vitro assays, a bacterial mutation assay and an in vitro chromosome aberration assay. Neither 4-cholesten-3-one nor 5??-cholestan-3-one showed evidence of mutagenic activity in these assays. ?? 2002 Elsevier Science Ltd. All rights reserved.
-
safety evaluation of Phytosterol esters part 1 assessment of oestrogenicity using a combination of in vivo and in vitro assays
Food and Chemical Toxicology, 1999Co-Authors: V A Baker, P. A. Hepburn, S J Kennedy, P A Jones, John P Sumpter, John AshbyAbstract:Abstract Phytosterols are natural constituents of the human diet, and as part of an extensive programme of safety evaluation studies investigating their use as a novel food ingredient, the possible oestrogenic effects of Phytosterols have been investigated using a combination of in vitro and in vivo assays. Competitive binding with the immature rat uterine oestrogen receptor (ER) has been used to measure the ability of Phytosterols to bind to ERs while the transcriptional activation of oestrogen-responsive genes has been examined in an oestrogen-inducible yeast screen. Phytosterols did not display any activity in these in vitro assays. Uterotrophic assays have been conducted to investigate the potential for Phytosterols to elicit an oestrogenic response when administered orally to immature female rats (n=10) at doses of 0, 5, 50 or 500 mg/kg/day for 3 consecutive days. Phytosterols (a well characterized mixture of β -sitosterol, campesterol and stigmasterol) and Phytosterol esters (the previous Phytosterol mixture esterified with fatty acids from sunflower oil) did not exhibit oestrogenic activity in the immature female rat using uterine wet weight as the endpoint. β -oestradiol (0.4 mg/kg/day) consistently produced a significant increase in uterus weights. Coumestrol (a known phytoestrogen) was also tested as a weak positive control and produced a dose response at doses of 20, 40 and 80 mg/kg/day in the uterotrophic assay. In conclusion, we have shown that Phytosterols do not bind to the ER and do not stimulate transcriptional activity of the human ER in a recombinant yeast strain. In addition, there was no indication of oestrogenicity from the uterotrophic assay when the material was administered by oral gavage to immature female rats.
A. M. Wolfreys - One of the best experts on this subject based on the ideXlab platform.
-
Safety evaluation of Phytosterol esters. Part 8. Lack of genotoxicity and subchronic toxicity with Phytosterol oxides.
Food and Chemical Toxicology, 2004Co-Authors: P. A. Hepburn, A. M. Wolfreys, Paul BaldrickAbstract:Vegetable oil spreads containing Phytosterol-esters are marketed as a cholesterol-lowering functional food in more than 20 countries worldwide. An extensive package of safety data has shown Phytosterol-esters to be safe for human use. However, even though Phytosterols are very stable molecules, oxidation may occur at low levels under extreme heating conditions, resulting in Phytosterol oxides. As there is some suggestion of adverse biological effects in the literature for the related cholesterol oxidation products, safety data have been generated for Phytosterol oxides. A Phytosterol oxide concentrate (POC) was generated by prolonged heating of Phytosterol-esters in the presence of oxygen. The genotoxicity and subchronic toxicity of this mixture was assessed in a series of in vitro genotoxicity assays (bacterial mutation, chromosome aberration and micronucleus) and a subchronic feeding study in the rat. Results showed that a Phytosterol oxide concentrate containing approximately 30% Phytosterol oxides did not possess genotoxic potential and no obvious evidence of toxicity when administered in the diet of the rat for 90 consecutive days. In the latter study, a NOEL was established at an estimated dietary level of Phytosterol oxides of 128 mg/kg/day for males and 144 mg/kg/day for females. In conclusion, these materials have been shown to raise no obvious concerns for human safety.
-
Safety evaluation of Phytosterol esters. Part 8. Lack of genotoxicity and subchronic toxicity with Phytosterol oxides
Food and Chemical Toxicology, 2004Co-Authors: L J Lea, P. A. Hepburn, A. M. Wolfreys, Paul BaldrickAbstract:Vegetable oil spreads containing Phytosterol-esters are marketed as a cholesterol-lowering functional food in more than 20 countries worldwide. An extensive package of safety data has shown Phytosterol-esters to be safe for human use. However, even though Phytosterols are very stable molecules, oxidation may occur at low levels under extreme heating conditions, resulting in Phytosterol oxides. As there is some suggestion of adverse biological effects in the literature for the related cholesterol oxidation products, safety data have been generated for Phytosterol oxides. A Phytosterol oxide concentrate (POC) was generated by prolonged heating of Phytosterol-esters in the presence of oxygen. The genotoxicity and subchronic toxicity of this mixture was assessed in a series of in vitro genotoxicity assays (bacterial mutation, chromosome aberration and micronucleus) and a subchronic feeding study in the rat. Results showed that a Phytosterol oxide concentrate containing approximately 30% Phytosterol oxides did not possess genotoxic potential and no obvious evidence of toxicity when administered in the diet of the rat for 90 consecutive days. In the latter study, a NOEL was established at an estimated dietary level of Phytosterol oxides of 128 mg/kg/day for males and 144 mg/kg/day for females. In conclusion, these materials have been shown to raise no obvious concerns for human safety. © 2004 Elsevier Ltd. All rights reserved.
-
Safety evaluation of Phytosterol esters. Part 7. Assessment of mutagenic activity of Phytosterols, Phytosterol esters and the cholesterol derivative, 4-cholesten-3-one
Food and Chemical Toxicology, 2002Co-Authors: A. M. Wolfreys, P. A. HepburnAbstract:Abstract Phytosterol esters are Phytosterols derived from vegetable oils following esterification to fatty acids. When Phytosterols are added to foods, they inhibit the absorption of dietary and endogenous cholesterol and thereby reduce blood cholesterol concentrations. As part of a comprehensive programme of safety assessment, the mutagenic potential of Phytosterols and Phytosterol esters has been assessed in a bacterial mutation assay and an in vitro chromosome aberration assay. In addition, an in vitro mammalian cell gene mutation assay and two in vivo mutagenicity studies, namely rat bone marrow micronucleus and liver unscheduled DNA synthesis (UDS) assays, were conducted on Phytosterol esters only. Phytosterols and Phytosterol esters did not show any evidence of mutagenic activity in any of these assays. A breakdown product of cholesterol is 4-cholesten-3-one and thus the amount of 4-cholesten-3-one in the gut may increase following supplementation of foods with Phytosterol-esters. 4-cholesten-3-one had been previously reported as mutagenic but, due to various shortcomings, these data could not be used to assess the mutagenic activity of 4-cholesten-3-one. The mutagenic activity of 4-cholesten-3-one and its major faecal by-products, 5β-cholestan-3-one, was assessed in two in vitro assays, a bacterial mutation assay and an in vitro chromosome aberration assay. Neither 4-cholesten-3-one nor 5β-cholestan-3-one showed evidence of mutagenic activity in these assays.
-
Safety evaluation of Phytosterol esters. Part 7. Assessment of mutagenic activity of Phytosterols, Phytosterol esters and the cholesterol derivative, 4-cholesten-3-one
Food and Chemical Toxicology, 2002Co-Authors: A. M. Wolfreys, P. A. HepburnAbstract:Phytosterol esters are Phytosterols derived from vegetable oils following esterification to fatty acids. When Phytosterols are added to foods, they inhibit the absorption of dietary and endogenous cholesterol and thereby reduce blood cholesterol concentrations. As part of a comprehensive programme of safety assessment, the mutagenic potential of Phytosterols and Phytosterol esters has been assessed in a bacterial mutation assay and an in vitro chromosome aberration assay. In addition, an in vitro mammalian cell gene mutation assay and two in vivo mutagenicity studies, namely rat bone marrow micronucleus and liver unscheduled DNA synthesis (UDS) assays, were conducted on Phytosterol esters only. Phytosterols and Phytosterol esters did not show any evidence of mutagenic activity in any of these assays. A breakdown product of cholesterol is 4-cholesten-3-one and thus the amount of 4-cholesten-3-one in the gut may increase following supplementation of foods with Phytosterol-esters. 4-cholesten-3-one had been previously reported as mutagenic but, due to various shortcomings, these data could not be used to assess the mutagenic activity of 4-cholesten-3-one. The mutagenic activity of 4-cholesten-3-one and its major faecal by-products, 5??-cholestan-3-one, was assessed in two in vitro assays, a bacterial mutation assay and an in vitro chromosome aberration assay. Neither 4-cholesten-3-one nor 5??-cholestan-3-one showed evidence of mutagenic activity in these assays. ?? 2002 Elsevier Science Ltd. All rights reserved.