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Walter C Willett - One of the best experts on this subject based on the ideXlab platform.
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Premenopausal dietary fat in relation to pre- and post-menopausal breast cancer
Breast Cancer Research and Treatment, 2014Co-Authors: Maryam S. Farvid, A. Heather Eliassen, Wendy Y Chen, Eunyoung Cho, Walter C WillettAbstract:We examined the association between fat Intake and breast cancer incidence in the Nurses' Health Study II. We followed 88,804 women aged 26-45 years from 1991 to 2011 and documented incident breast cancers. Dietary fat, assessed by questionnaires in 1991, was examined in relation to total, premenopausal, and postmenopausal breast cancers. Multivariable-adjusted Cox proportional hazards models were used to estimate relative risk (RR) and 95 % confidence intervals (95 % CI). During 20 years of follow-up, 2,830 incident invasive breast cancer cases were diagnosed. Total fat Intake was not associated with risk of breast cancer overall. After adjustment for demographic, anthropometric, lifestyle, and dietary factors, a positive association was observed between animal fat Intake and breast cancer overall (RR for highest vs lowest quintile, 1.18; 95 % CI 1.04-1.33; P trend = 0.01). A positive association with animal fat Intake was also seen among premenopausal women, but not among postmenopausal women. Higher Intakes of saturated fat and monounsaturated fat were each associated with modestly higher breast cancer risk among all women, and higher Cholesterol Intake was associated with higher premenopausal breast cancer risk. However, the associations of saturated fat, monounsaturated fat and animal fat, were attenuated and non-significant after adjustment for red meat Intake. Intakes of other types of fat including vegetable fat, dairy fat, polyunsaturated fat, and trans fat were not associated with breast cancer risk. Our finding suggests a positive association between early adult Intake of animal fat and breast cancer risk.
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abstract 144 dietary fat and Cholesterol Intake in relation to fatal breast cancer
Cancer Research, 2013Co-Authors: Caroline E Boeke, Wendy Y Chen, Eunyoung Cho, Walter C Willett, Heather A Eliassen, Michelle D Holmes, Bernard Rosner, Rulla M TamimiAbstract:Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Dietary fats are not strongly associated with breast cancer incidence in general, but it is unknown whether fat Intake influences risk of developing more aggressive, fatal breast cancer. We evaluated Intake of total fat, specific types of fat (saturated, monounsaturated, polyunsaturated, trans fat; omega 3 polyunsaturated; animal and vegetable), and Cholesterol prior to cancer diagnosis in relation to fatal breast cancer risk in 88,627 women in the Nurses’ Health Study (NHS; 1980-2008) and 93,372 women in the Nurses’ Health Study II (NHS II; 1991-2009). Diet was assessed every 4 years using a semi-quantitative food frequency questionnaire. Breast cancer cases were confirmed with pathology reports and deaths were confirmed using the National Death Index. We calculated cumulative average percent calories from fat Intake and used substitution models to adjust for macronutrient composition. For Cholesterol, we adjusted for total energy Intake using the residual method. We defined fatal cases as women with breast cancer who died and had breast cancer listed as their primary cause of death. There were 1149 fatal breast cancer cases in NHS and 206 fatal cases in NHS II. After adjusting for multiple risk factors for breast cancer, neither total fat nor types of fat were associated with risk of fatal breast cancer in NHS or NHS II. For example, compared with those in the lowest quintile of saturated fat Intake, those in the highest quintile had a hazard ratio (HR) of 1.02 (95% CI: 0.75, 1.38; p-trend=0.80) in NHS and 1.14 (0.61, 2.13; p-trend=0.61) in NHS II. In NHS there was a suggestive positive association between Cholesterol and fatal breast cancer (Q5 vs. Q1 HR: 1.28, 95% CI: 1.02, 1.61; p-trend=0.04); this association did not persist in NHS II (0.73; 95% CI: 0.41, 1.32; p-trend=0.44) but should be examined further. Long-term pre-diagnosis dietary fat Intake was not associated with fatal breast cancer in these two large prospective cohort studies. View this table: Cholesterol and percent calories from fat in relation to fatal breast cancer, Nurses” Health Study. Citation Format: Caroline E. Boeke, A. Heather Eliassen, Wendy Y. Chen, Eunyoung Cho, Michelle D. Holmes, Bernard Rosner, Walter C. Willett, Rulla M. Tamimi. Dietary fat and Cholesterol Intake in relation to fatal breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 144. doi:10.1158/1538-7445.AM2013-144
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risk factors for mortality in the nurses health study a competing risks analysis
American Journal of Epidemiology, 2011Co-Authors: Heather J Baer, Walter C Willett, Meir J Stampfer, Graham A Colditz, Robert J Glynn, Susan E Hankinson, Bernard RosnerAbstract:Few studies have examined multiple risk factors for mortality or formally compared their associations across specific causes of death. The authors used competing risks survival analysis to evaluate associations of lifestyle and dietary factors with all-cause and cause-specific mortality among 50,112 participants in the Nurses' Health Study. There were 4,893 deaths between 1986 and 2004: 1,026 from cardiovascular disease, 931 from smoking-related cancers, 1,430 from cancers not related to smoking, and 1,506 from all other causes. Age, body mass index at age 18 years, weight change, height, current smoking and pack-years of smoking, glycemic load, Cholesterol Intake, systolic blood pressure and use of blood pressure medications, diabetes, parental myocardial infarction before age 60 years, and time since menopause were directly related to all-cause mortality, whereas there were inverse associations for physical activity and Intakes of nuts, polyunsaturated fat, and cereal fiber. Moderate alcohol consumption was associated with decreased mortality. A model that incorporated differences in the associations of some risk factors with specific causes of death had a significantly better fit compared with a model in which all risk factors had common associations across all causes. In the future, this new model may be used to identify individuals at increased risk of mortality.
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dietary fat Intake and the risk of coronary heart disease in women
The New England Journal of Medicine, 1997Co-Authors: Meir J Stampfer, Bernard Rosner, Joann E Manson, Eric B Rimm, Graham A Colditz, Charles H Hennekens, Walter C WillettAbstract:Background The relation between dietary Intake of specific types of fat, particularly trans unsaturated fat, and the risk of coronary disease remains unclear. We therefore studied this relation in women enrolled in the Nurses' Health Study. Methods We prospectively studied 80,082 women who were 34 to 59 years of age and had no known coronary disease, stroke, cancer, hyperCholesterolemia, or diabetes in 1980. Information on diet was obtained at base line and updated during follow-up by means of validated questionnaires. During 14 years of follow-up, we documented 939 cases of nonfatal myocardial infarction or death from coronary heart disease. Multivariate analyses included age, smoking status, total energy Intake, dietary Cholesterol Intake, percentages of energy obtained from protein and specific types of fat, and other risk factors. Results Each increase of 5 percent of energy Intake from saturated fat, as compared with equivalent energy Intake from carbohydrates, was associated with a 17 percent increa...
Albert K. Groen - One of the best experts on this subject based on the ideXlab platform.
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ezetimibe stimulates faecal neutral sterol excretion depending on abcg8 function in mice
FEBS Letters, 2010Co-Authors: Lily Jakulj, Maud N Vissers, Cindy P A A Van Roomen, Jelske N Van Der Veen, Carlos L J Vrins, Cindy Kunne, John J. P. Kastelein, Frans Stellaard, Albert K. GroenAbstract:Ezetimibe stimulates faecal neutral sterol (FNS) excretion in mice, which cannot be explained by Cholesterol absorption inhibition alone. We investigated whether these effects are mediated via the sterol exporter ATP binding cassette transporter G8 (abcg8). Ezetimibe increased FNS excretion 2.7-fold in WT mice and 1.5-fold in abcg8−/− mice, without affecting biliary Cholesterol secretion. Daily FNS excretion exceeded the sum of dietary Cholesterol Intake and biliary secretion by about 60%. Ezetimibe enhanced this ‘extra’ FNS excretion by 3.5-fold and 1.5-fold in wildtype (WT) and abcg8−/− mice, respectively. Ezetimibe stimulates fecal sterol excretion of non-biliary and non-dietary origin, probably through stimulation of trans-intestinal Cholesterol excretion. We show that this effect depends on intact abcg8 function.
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direct intestinal Cholesterol secretion contributes significantly to total fecal neutral sterol excretion in mice
Gastroenterology, 2007Co-Authors: Astrid E Van Der Velde, Carlos L J Vrins, Cindy Kunne, Karin Van Den Oever, Ronald Oude P J Elferink, Folkert Kuipers, Albert K. GroenAbstract:Background & Aims: Hepatobiliary secretion is generally believed to be an integral step in the pathway of Cholesterol excretion from the body. Here we have investigated the validity of this paradigm in mice. Methods: Cholesterol balance was assessed by measuring Intake, excretion, and biliary output in different mouse models. Direct secretion of Cholesterol from the luminal side of enterocytes was studied by perfusion of isolated segments of the small intestine in mice. Results: Cholesterol input and output measurements in different mouse models revealed that fecal neutral sterol excretion was higher than the sum of dietary Cholesterol Intake and biliary Cholesterol secretion indicating the existence of an alternative pathway. Here we show that substantial amounts of Cholesterol can be secreted directly by enterocytes. Transintestinal Cholesterol secretion is a specific process observed throughout the small intestine (proximal > medial > distal). Secretion depended on the presence of a Cholesterol acceptor and was strongly stimulated by bile salts and phospholipids. The capacity of the pathway was sufficient to account for the missing Cholesterol in the balance studies. The contribution of this pathway to Cholesterol excretion in mice is approximately twice that of the biliary pathway. Conclusions: In mice, the intestine plays a significant role in removal of Cholesterol from the body.
Martijn B. Katan - One of the best experts on this subject based on the ideXlab platform.
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dietary Cholesterol from eggs increases the ratio of total Cholesterol to high density lipoprotein Cholesterol in humans a meta analysis
The American Journal of Clinical Nutrition, 2001Co-Authors: R M Weggemans, Peter L Zock, Martijn B. KatanAbstract:Several epidemiologic studies found no effect of egg consumption on the risk of coronary heart disease. It is possible that the adverse effect of eggs on LDL-Cholesterol is offset by their favorable effect on HDL Cholesterol. Objective: The objective was to review the effect of dietary Cholesterol on the ratio of total to HDL Cholesterol. Design: Studies were identified by MEDLINE and Biological Abstracts searches (from 1974 to June 1999) and by reviewing reference lists. In addition, we included data from a more recently published study. Studies were included if they had a crossover or parallel design with a control group, if the experimental diets differed only in the amount of dietary Cholesterol or number of eggs and were fed for ≥ 14 d, and if HDL-Cholesterol concentrations were reported. Of the 222 studies identified, 17 studies involving 556 subjects met these criteria. Results: The addition of 100 mg dietary Cholesterol/d increased the ratio of total to HDL Cholesterol by 0.020 units (95␌I: 0.010, 0.030), total Cholesterol concentrations by 0.056 mmol/L (2.2 mg/dL) (95␌I: 0.046, 0.065 mmol/L; 1.8, 2.5 mg/dL), and HDL-Cholesterol concentrations by 0.008 mmol/L (0.3 mg/dL) (95␌I: 0.005, 0.010 mmol/L; 0.2, 0.4 mg/dL). Conclusions: Dietary Cholesterol raises the ratio of total to HDL Cholesterol and, therefore, adversely affects the Cholesterol profile. The advice to limit Cholesterol Intake by reducing consumption of eggs and other Cholesterol-rich foods may therefore still be valid.
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dietary saturated fatty acids increase Cholesterol synthesis and fecal steroid excretion in healthy men and women
European Journal of Clinical Investigation, 1993Co-Authors: Jan F. C. Glatz, Martijn B. KatanAbstract:. In a strictly controlled 6-week trial with 47 healthy volunteers we have determined the effect of replacement of polyunsaturated by saturated fatty acids on the fecal steroid excretion and on the rate of whole body Cholesterol synthesis, as measured both by the sterol balance method and by the concentration of the Cholesterol precursor lathosterol in serum. Subjects were fed mixed natural diets, of which the total fat content was kept constant at 45% energy. Consumption of polyunsaturated fatty acids, mainly linoleic acid, was 21 % energy for the first 3-week period (P: S ratio 1.9), and 5% of energy (P: S ratio 0.2) for the next 3-week period, or vice versa. Cholesterol Intake as determined by analysis of duplicate diets was 41 mg MJ-1 (about 500 mg day-1) during both periods. Feces were collected for 5 days at the end of both periods. The steroid composition of the feces was not affected by the change of diets. The fecal excretion of neutral steroids was significantly higher on the low P: S high-saturated-fat (2.25 ± 0.68 mmol day-1) than on the high P:S high-linoleic-acid diet (2.00 ± 0.69 mmol day-1; P < 0.01). The excretion of bile acids was similar (0.77 ± 0.40 and 0.79 ± 0.41 mmol day-1, respectively). The Cholesterol balance and the rate of Cholesterol synthesis were higher during the low P:S (1.86 ± 0.83 mmol day-1) than during the high P:S period (1.55 ± 0.85 mmol day-1; P < 0.01). The ratio of lathosterol to Cholesterol in serum was 0.86 ± 0.33 μmol mmol-1 on the high-and 1.07 ± 0.39 μmol mmol-1 on the low P: S diet (P < 0.01). Thus, both the balance and the Cholesterol precursor method suggested that saturated fatty acids stimulate whole-body Cholesterol synthesis.
Kevin Taddei - One of the best experts on this subject based on the ideXlab platform.
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the guinea pig as a model for sporadic alzheimer s disease ad the impact of Cholesterol Intake on expression of ad related genes
PLOS ONE, 2013Co-Authors: Mathew J Sharman, Seyyed Hani Moussavi Nik, Mengqi M Chen, Daniel Ong, Linda K Wijaya, Simon M Laws, Kevin TaddeiAbstract:We investigated the guinea pig, Cavia porcellus, as a model for Alzheimer’s disease (AD), both in terms of the conservation of genes involved in AD and the regulatory responses of these to a known AD risk factor - high Cholesterol Intake. Unlike rats and mice, guinea pigs possess an Aβ peptide sequence identical to human Aβ. Consistent with the commonality between cardiovascular and AD risk factors in humans, we saw that a high Cholesterol diet leads to up-regulation of BACE1 (β-secretase) transcription and down-regulation of ADAM10 (α-secretase) transcription which should increase release of Aβ from APP. Significantly, guinea pigs possess isoforms of AD-related genes found in humans but not present in mice or rats. For example, we discovered that the truncated PS2V isoform of human PSEN2, that is found at raised levels in AD brains and that increases γ-secretase activity and Aβ synthesis, is not uniquely human or aberrant as previously believed. We show that PS2V formation is up-regulated by hypoxia and a high-Cholesterol diet while, consistent with observations in humans, Aβ concentrations are raised in some brain regions but not others. Also like humans, but unlike mice, the guinea pig gene encoding tau, MAPT, encodes isoforms with both three and four microtubule binding domains, and Cholesterol alters the ratio of these isoforms. We conclude that AD-related genes are highly conserved and more similar to human than the rat or mouse. Guinea pigs represent a superior rodent model for analysis of the impact of dietary factors such as Cholesterol on the regulation of AD-related genes.
Cindy Kunne - One of the best experts on this subject based on the ideXlab platform.
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ezetimibe stimulates faecal neutral sterol excretion depending on abcg8 function in mice
FEBS Letters, 2010Co-Authors: Lily Jakulj, Maud N Vissers, Cindy P A A Van Roomen, Jelske N Van Der Veen, Carlos L J Vrins, Cindy Kunne, John J. P. Kastelein, Frans Stellaard, Albert K. GroenAbstract:Ezetimibe stimulates faecal neutral sterol (FNS) excretion in mice, which cannot be explained by Cholesterol absorption inhibition alone. We investigated whether these effects are mediated via the sterol exporter ATP binding cassette transporter G8 (abcg8). Ezetimibe increased FNS excretion 2.7-fold in WT mice and 1.5-fold in abcg8−/− mice, without affecting biliary Cholesterol secretion. Daily FNS excretion exceeded the sum of dietary Cholesterol Intake and biliary secretion by about 60%. Ezetimibe enhanced this ‘extra’ FNS excretion by 3.5-fold and 1.5-fold in wildtype (WT) and abcg8−/− mice, respectively. Ezetimibe stimulates fecal sterol excretion of non-biliary and non-dietary origin, probably through stimulation of trans-intestinal Cholesterol excretion. We show that this effect depends on intact abcg8 function.
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direct intestinal Cholesterol secretion contributes significantly to total fecal neutral sterol excretion in mice
Gastroenterology, 2007Co-Authors: Astrid E Van Der Velde, Carlos L J Vrins, Cindy Kunne, Karin Van Den Oever, Ronald Oude P J Elferink, Folkert Kuipers, Albert K. GroenAbstract:Background & Aims: Hepatobiliary secretion is generally believed to be an integral step in the pathway of Cholesterol excretion from the body. Here we have investigated the validity of this paradigm in mice. Methods: Cholesterol balance was assessed by measuring Intake, excretion, and biliary output in different mouse models. Direct secretion of Cholesterol from the luminal side of enterocytes was studied by perfusion of isolated segments of the small intestine in mice. Results: Cholesterol input and output measurements in different mouse models revealed that fecal neutral sterol excretion was higher than the sum of dietary Cholesterol Intake and biliary Cholesterol secretion indicating the existence of an alternative pathway. Here we show that substantial amounts of Cholesterol can be secreted directly by enterocytes. Transintestinal Cholesterol secretion is a specific process observed throughout the small intestine (proximal > medial > distal). Secretion depended on the presence of a Cholesterol acceptor and was strongly stimulated by bile salts and phospholipids. The capacity of the pathway was sufficient to account for the missing Cholesterol in the balance studies. The contribution of this pathway to Cholesterol excretion in mice is approximately twice that of the biliary pathway. Conclusions: In mice, the intestine plays a significant role in removal of Cholesterol from the body.