Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Distinct Longitudinal Associations of MBL, MASP-1, MASP-2, MASP-3, and MAp44 With Endothelial Dysfunction and Intima-Media Thickness: The CODAM Study
Hertle, E. ; Arts, I.C.W. ; Kallen, C.J.H. van der; Feskens, E.J.M. ; Schalkwijk, C.G. ; Hoffmann-Petersen, I. ; Thiel, S. ; Stehouwer, C.D. ; Greevenbroek, M.M. - \ 2016
Arteriosclerosis Thrombosis and Vascular Biology 36 (2016)6. - ISSN 1079-5642 - p. 1278 - 1285.
Previous studies suggested that the lectin-complement pathway plays a complex role in cardiovascular disease (CVD). To date, no prospective human studies have investigated the relationship between the initiating factor of the lectin pathway, that is, mannose-binding lectin (MBL), and low-grade inflammation, endothelial dysfunction, or carotid intima–media thickness (cIMT). Moreover, MBL-associated proteases (MASPs) and MBL-associated proteins (MAps), which mediate downstream complement activation, have not been studied in the development of CVD.
The cross-sectional association between uric acid and atherosclerosis and the role of low-grade inflammation: the CODAM study
Wijnands, J.M.A. ; Boonen, A. ; Dagnelie, P.C. ; Greevenbroek, M.M.J. van; Kallen, C.J.H. van der; Ferreira, I. ; Schalkwijk, C.G. ; Feskens, E.J.M. ; Stehouwer, C.D.A. ; Linden, S. van der; Arts, I.C.W. - \ 2014
RHEUMATOLOGY 53 (2014)11. - ISSN 1462-0324 - p. 2053 - 2062.
peripheral arterial-disease - c-reactive protein - type-2 diabetes-mellitus - nitric-oxide production - metabolic syndrome - carotid atherosclerosis - cardiovascular-disease - hypertensive patients - risk-factor - subclinical atherosclerosis
Objectives. The aims of this study were to investigate (i) associations between uric acid and prevalent cardiovascular disease (CVD), ankle-arm blood pressure index (AAIx) and carotid intima-media thickness (CIMT) in the total population and in predefined subgroups according to glucose metabolism status and (ii) the extent to which these associations are explained by low-grade inflammation. Methods. Cross-sectional analyses were conducted among 530 individuals [60.6% men, mean age 58.9 years (S. D. 6.9), 52.6% normal glucose metabolism (NGM)] at increased risk of CVD from the Cohort of Diabetes and Atherosclerosis Maastricht study. A low-grade inflammation score was computed by averaging the z-scores of eight inflammation markers [CRP, TNF-alpha, IL-6, IL-8, serum amyloid A, intercellular adhesion molecule 1 (ICAM-1), ceruloplasmin and haptoglobin]. Results. After adjustment for traditional CVD risk factors, plasma uric acid (per S. D. of 81 mu mol/l) was associated with CVD in individuals with NGM [odds ratio (OR) = 1.66, 95% CI 1.06, 2.58] but not with disturbed glucose metabolism (DGM) (OR = 0.81, 95% CI 0.55, 1.19, P interaction = 0.165). Uric acid was associated with CIMT in the total population (beta = 0.024, 95% CI 0.007, 0.042) and slightly more strongly in individuals with NGM (beta = 0.030, 95% CI 0.006, 0.054) than DGM (beta = 0.018, 95% CI -0.009, 0.044, P interaction = 0.443). There was no association between uric acid and AAIx in any group (P interaction = 0.058). Uric acid was associated with low-grade inflammation in the total population (beta = 0.074, 95% CI 0.013, 0.134, P interaction = 0.737). Adding low-grade inflammation to the models did not attenuate any of the associations. Conclusion. The associations for uric acid with CIMT, and with CVD in NGM only, were not explained by low-grade inflammation. A difference in the strength of the associations between individuals with NGM and DGM was suggested.
Letter to the Editor : Complement activation products C5a and sC5b-9 are associated with low-grade inflammation and endothelial dysfunciton, but not with atherosclerosis in a cross-sectional analysis: The CODAM study
Hertle, E. ; Greevenbroek, M.M.J. van; Arts, I.C.W. ; Kallen, C.J.H. van der; Feskens, E.J.M. ; Schalkwijk, C.G. ; Stehouwer, C.D.A. - \ 2014
International Journal of Cardiology 174 (2014)2. - ISSN 0167-5273 - p. 400 - 403.
membrane attack complex - cardiovascular events - myocardial-infarction - cells - system
Distinct associations of complement C3a and its precursor C3 with atherosclerosis and cardiovascular disease
Hertle, E. ; Greevenbroek, M.M.J. van; Arts, I.C.W. ; Kallen, C.J.H. van der; Geijselaers, S.L.C. ; Feskens, E.J.M. ; Jansen, E.H. ; Schalkwijk, C.G. ; Stehouwer, C.D.A. - \ 2014
Thrombosis and Haemostasis 111 (2014)6. - ISSN 0340-6245 - p. 1102 - 1111.
coronary-artery-disease - acylation-stimulating protein - intima-media thickness - low-grade inflammation - metabolic syndrome - anaphylatoxins c3a - insulin-resistance - diabetes-mellitus - endothelial-cells - cigarette-smoke
Complement C3 is a novel risk factor for cardiovascular disease (CVD), but the underlying mechanism is currently unknown. We determined the associations of the anaphylatoxin C3a, the activation product of C3, and of C3 itself with estimates of atherosclerosis and CVD. We studied associations of C3a and C3 with carotid intima-media thickness (cIMT), ankle-arm blood pressure index (AAIx) and CVD in cross-sectional analyses among 545 participants of the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study (61% men, 59.4 ± 6.9 years) and examined effect modification by smoking. We conducted linear and logistic regression analyses with adjustments for age, sex, glucose metabolism status, lipids, adiposity, renal function, blood pressure, pack-years smoked, physical activity, use of medication and investigated mediation by inflammation. C3a was independently associated with cIMT (ß=0.032 mm, [95% confidence interval: 0.004; 0.060]) and AAIx (ß=-0.022, [-0.043; –0.001]), but C3 was not. Effect modification by smoking was only observed for CVD (Psmoking*C3a=0.008, Psmoking*C3=0.018), therefore these associations were stratified for smoking behaviour. Both C3a (odds ratio [OR] =2.96, [1.15; 7.62]) and C3 (OR =1.98, [1.21; 3.22]) were independently associated with CVD in heavy smokers. The association of C3 with CVD was independent of C3a. Low-grade inflammation did partially explain the association of C3a with AAIx, but not the other observed associations. This suggests that C3a and C3 have distinct roles in pathways leading to CVD. C3a may promote atherosclerosis and additionally advance CVD in heavy smokers. Conversely, C3 may be associated with CVD in heavy smokers via pathways other than atherosclerosis.
Complement C3 is inversely associated with habitual intake of provitamin A but not with dietary fat, fatty acids, or vitamin E in Middle-aged to older white adults and positively associated with intake of retinol in middle-aged to older white women
Greevenbroek, M.M. ; Arts, I.C.W. ; Kallen, C.J.H. van der; Dagnelie, P.C. ; Ferreira, I. ; Jansen, G.H.E. ; Schalkwijk, C.G. ; Feskens, E.J.M. ; Stehouwer, C.D.A. - \ 2014
The Journal of Nutrition 144 (2014)1. - ISSN 0022-3166 - p. 61 - 67.
population-based cohort - myocardial-infarction - a supplementation - serum c3 - insulin-resistance - relative validity - immune-system - disease - risk - protein
Complement factor 3 (C3) has been identified as a novel risk factor for obesity-associated cardiometabolic diseases. Data in the literature suggest that C3 concentrations may be influenced by diet. Therefore, we investigated the associations of intake of total fat, specific fatty acids, and fat-soluble vitamin E (and individual tocopherols) and vitamin A (and its dietary precursors) with circulating C3. In a white cohort [Cohort on Diabetes and Atherosclerosis Maastricht (CODAM)]; n = 501; 59.4 ± 7.1 y; 61% men], associations of habitual nutrient intake (assessed by a food-frequency questionnaire) with circulating C3 were evaluated by using cross-sectional multiple linear regression analyses. Adjustments were first performed for age, sex, glucose metabolism status (i.e., impaired glucose metabolism or type 2 diabetes), and energy intake and subsequently for BMI, waist circumference, alcohol intake, smoking behavior, and season of blood collection. No associations with C3 were observed for total dietary fat intake or intake of specific fatty acids [saturated, monounsaturated, polyunsaturated, n–6 (¿6), and n–3 (¿3) fatty acids], vitamin E, or individual tocopherols. We observed an inverse association with intake of provitamin A carotenoids a-carotene (in µg/d; regression coefficient ß = -0.075; 95% CI: -0.140, -0.010; P = 0.025) and ß-carotene (in µg/d; ß = -0.021; 95% CI: -0.044, 0.002; P = 0.068) with C3 (in mg/L). In contrast, and only in women, dietary retinol intake (in µg/d) was positively associated with C3 (ß = 0.116; 95% CI: 0.014, 0.218; P = 0.026; n = 196). In conclusion, these data suggest that fasting concentrations of C3 may, in a complex manner, be modifiable by variation in dietary provitamin A carotenoids and/or retinol content of the usual diet but most likely not by variations in fat composition and vitamin E content.
Adenosine 5 '-triphosphate (ATP) supplements are not orally bioavailable: a randomized, placebo-controlled cross-over trial in healthy humans
Arts, I.C.W. ; Coolen, E.J.C.M. ; Bours, M.J.L. ; Huyghebaert, N. ; Cohen Stuart, M.A. ; Bast, A. ; Dagnelie, P.C. - \ 2012
Journal of the International Society of Sports Nutrition 9 (2012). - ISSN 1550-2783
low-back-pain - uric-acid - nucleoside transporters - cancer-patients - small-intestine - crohns-disease - nucleotide - triphosphate - transit - urate
Background: Nutritional supplements designed to increase adenosine 5'-triphosphate (ATP) concentrations are commonly used by athletes as ergogenic aids. ATP is the primary source of energy for the cells, and supplementation may enhance the ability to maintain high ATP turnover during high-intensity exercise. Oral ATP supplements have beneficial effects in some but not all studies examining physical performance. One of the remaining questions is whether orally administered ATP is bioavailable. We investigated whether acute supplementation with oral ATP administered as enteric-coated pellets led to increased concentrations of ATP or its metabolites in the circulation. Methods: Eight healthy volunteers participated in a cross-over study. Participants were given in random order single doses of 5000 mg ATP or placebo. To prevent degradation of ATP in the acidic environment of the stomach, the supplement was administered via two types of pH-sensitive, enteric-coated pellets (targeted at release in the proximal or distal small intestine), or via a naso-duodenal tube. Blood ATP and metabolite concentrations were monitored by HPLC for 4.5 h (naso-duodenal tube) or 7 h (pellets) post-administration. Areas under the concentration vs. time curve were calculated and compared by paired-samples t-tests. Results: ATP concentrations in blood did not increase after ATP supplementation via enteric-coated pellets or naso-duodenal tube. In contrast, concentrations of the final catabolic product of ATP, uric acid, were significantly increased compared to placebo by similar to 50% after administration via proximal-release pellets (P = 0.003) and naso-duodenal tube (P = 0.001), but not after administration via distal-release pellets. Conclusions: A single dose of orally administered ATP is not bioavailable, and this may explain why several studies did not find ergogenic effects of oral ATP supplementation. On the other hand, increases in uric acid after release of ATP in the proximal part of the small intestine suggest that ATP or one of its metabolites is absorbed and metabolized. Uric acid itself may have ergogenic effects, but this needs further study. Also, more studies are needed to determine whether chronic administration of ATP will enhance its oral bioavailability.
Deconjugation Kinetics of Glucuronidated Phase II Flavonoid Metabolites by B-glucuronidase from Neutrophils
Bartholomé, R. ; Haenen, G. ; Hollman, P.C.H. ; Bast, A. ; Dagnelie, P.C. ; Roos, D. ; Keijer, J. ; Kroon, P.A. ; Needs, P.W. ; Arts, I.C.W. - \ 2010
Drug Metabolism and Pharmacokinetics 25 (2010)4. - ISSN 1347-4367 - p. 379 - 387.
quercetin glucuronides - grain dust - inflammation - dietary - ph - tissue - cells - fluid - quercetin-4'-glucoside - quercetin-3-glucoside
Flavonoids are inactivated by phase II metabolism and occur in the body as glucuronides. Mammalian ß-glucuronidase released from neutrophils at inflammatory sites may be able to deconjugate and thus activate flavonoid glucuronides. We have studied deconjugation kinetics and pH optimum for four sources of ß-glucuronidase (human neutrophil, human recombinant, myeloid PLB-985 cells, Helix pomatia) with five flavonoid glucuronides (quercetin-3-glucuronide, quercetin-3'-glucuronide, quercetin-4'-glucuronide, quercetin-7-glucuronide, 3'-methylquercetin-3-glucuronide), 4-methylumbelliferyl-ß-D-glucuronide, and para-nitrophenol-glucuronide. All substrate-enzyme combinations tested exhibited first order kinetics. The optimum pH for hydrolysis was between 3.5-5, with appreciable hydrolysis activities up to pH 5.5. At pH 4, the Km ranged 44-fold from 22 µM for quercetin-4'-glucuronide with Helix pomatia ß-glucuronidase, to 981 µM for para-nitrophenol-glucuronide with recombinant ß-glucuronidase. Vmax (range: 0.735-24.012 µmol·min-1·unit-1 [1 unit is defined as the release of 1 µM 4-methylumbelliferyl-ß-D-glucuronide per min]) and the reaction rate constants at low substrate concentrations (k) (range: 0.002-0.062 min-1·(unit/L)-1 were similar for all substrates-enzyme combinations tested. In conclusion, we show that ß-glucuronidase from four different sources, including human neutrophils, is able to deconjugate flavonoid glucuronides and non-flavonoid substrates at fairly similar kinetic rates. At inflammatory sites in vivo the pH, neutrophil and flavonoid glucuronide concentrations seem favorable for deconjugation. However, it remains to be confirmed whether this is actually the case.
Some Phenolic Compounds Increase the Nitric Oxide Level in Endothelial Cells in Vitro
Appeldoorn, M.M. ; Venema, D.P. ; Peters, T.H.F. ; Koenen, M.E. ; Arts, I.C.W. ; Vincken, J.P. ; Gruppen, H. ; Keijer, J. ; Hollman, P.C.H. - \ 2009
Journal of Agricultural and Food Chemistry 57 (2009)17. - ISSN 0021-8561 - p. 7693 - 7699.
rat thoracic aorta - dependent relaxation - red wine - blood-pressure - peanut skins - grape seeds - green tea - flavonoids - synthase - cocoa
The vasorelaxing properties of chocolate and wine might relate to the presence of phenolic compounds. One of the potential mechanisms involved is stimulation of endothelial nitric oxide (NO) production, as NO is a major regulator of vasodilatation. This study aimed to develop an in vitro assay using the hybrid human endothelial cell line EA.hy926 to rapidly screen phenolic compounds for their NO-stimulating potential. The assay was optimized, and a selection of 33 phenolics, namely, procyanidins, monomeric flavan-3-ols, flavonols, a flavone, a flavanone, a chalcone, a stilbene, and phenolic acids, was tested for their ability to enhance endothelial NO level. Resveratrol, a well-known enhancer of NO level, was included as a positive control. Of the 33 phenolics tested, only resveratrol (285% increase in NO level), quercetin (110% increase), epicatechingallate (ECg) (85% increase), and epigallocatechingallate (EGCg) (60% increase) were significant (P = 0.05) enhancers. Procyanidins showed a nonsignificant tendency to elevate NO level. Concentration-dependent correlations between enhanced NO level and endothelial nitric oxide synthase (eNOS) expression were demonstrated for the three polyphenols tested (resveratrol, ECg, and EGCg). Thus, an easy screening tool for change in cellular NO level was developed. Use of this assay showed that only a limited number of phenolic compounds might enhance NO level with an increased amount of eNOS enzyme as a possible contributing mechanism.
Plasma enterolignans are not associated with nonfatal myocardial infarction risk
Kuijsten, A. ; Bueno-de-Mesquita, H.B. ; Boer, J.M.A. ; Arts, I.C.W. ; Kok, F.J. ; Veer, P. van 't; Hollman, P.C.H. - \ 2009
Atherosclerosis 203 (2009)1. - ISSN 0021-9150 - p. 145 - 152.
serum enterolactone concentration - cardiovascular-disease - postmenopausal women - cholesterol determination - dietary phytoestrogens - mass-spectrometry - flaxseed - secoisolariciresinol - lignans - chromatography
Plant lignans present in foods such as whole grains, seeds and nuts, fruits and vegetables, and beverages. Plant lignans are converted by intestinal bacteria into the enterolignans enterodiol and enterolactone. Up to now, epidemiological evidence for a protective role of enterolignans on cardiovascular diseases is limited and inconsistent. We investigated the association between plasma enterodiol and enterolactone and nonfatal myocardial infarction risk in a prospective study. During follow-up (1987-1998) of 15,107 subjects, aged 20-59 years, 236 incident nonfatal myocardial infarction cases were diagnosed. Controls (n = 283) were frequency matched to the cases on age, sex, and study center. No statistically significant associations between plasma enterodiol and enterolactone and risk of nonfatal myocardial infarction were detected. The odds ratio for the highest versus the lowest quartile of enterodiol was 1.21 (95% confidence interval (CI): 0.70, 2.12; p for trend = 0.74), and that of enterolactone 1.51 (95% CI: 0.87, 2.61; p for trend = 0.12) after adjustment for known dietary risk factors for coronary heart disease. No effect modification was observed for sex, menopausal status, or smoking status. Our results do not support the hypothesis that high plasma enterodiol or enterolactone concentrations are associated with a reduced risk of nonfatal myocardial infarction
Simultaneous determination of adenosine triphosphate and its metabolites in human whole blood by RP-HPLC and UV detection
Coolen, E.J.C.M. ; Arts, I.C.W. ; Swennen, E.L.R. ; Bast, A. ; Cohen Stuart, M.A. ; Dagnelie, P.C. - \ 2008
Journal of Chromatography. B, Analytical technologies in the biomedical and life sciences 864 (2008)1-2. - ISSN 1570-0232 - p. 43 - 51.
performance liquid-chromatography - myocardial adenine-nucleotides - reversed-phase - xanthine-oxidase - in-vitro - degradation products - creatine-phosphate - human-erythrocytes - purine metabolism - extracellular atp
To obtain insight in mechanisms of action of extracellular adenosine triphosphate (ATP) and adenosine, a simple HPLC method has been optimized and applied to investigate ATP metabolism in human whole blood ex vivo. This method provided good chromatographic resolution and peak shape for all eight compounds within a 19 min run time. The baseline was clean, the lower limit of quantification was below 0.3 micromol/L for all adenine nucleotides and the method demonstrated good linearity. Within-day precision ranged from 0.7 to 5.9% and between-days from 2.6 to 15.3%. Simplicity and simultaneous detection of ATP and its metabolites make this method suitable for clinical pharmacokinetic studies.
Plasma Enterolignan Concentrations and Colorectal Cancer Risk in a Nested Case-Control Study
Kuijsten, A. ; Hollman, P.C.H. ; Boshuizen, H.C. ; Buijsman, M.N.C.P. ; Veer, P. van 't; Kok, F.J. ; Arts, I.C.W. ; Bueno-de-Mesquita, H.B. - \ 2008
American Journal of Epidemiology 167 (2008)6. - ISSN 0002-9262 - p. 734 - 742.
serum enterolactone concentration - breast-cancer - mammalian lignans - circulating enterolactone - dietary phytoestrogens - netherlands cohort - rectal-cancer - colon-cancer - enterodiol - flaxseed
Enterolignans are biphenolic compounds that possess several biologic activities whereby they may influence carcinogenesis. The authors investigated the association between plasma enterolactone and enterodiol and colorectal cancer risk in a Dutch prospective study. Among more than 35,000 participants aged 20¿59 years, 160 colorectal cancer cases were diagnosed after 7.5 years of follow-up (1987¿2003). Cohort members who were frequency-matched to the cases on age, sex, and study center were selected as controls (n ¼ 387). Plasma enterodiol and enterolactone were not associated with risk of colorectal cancer after adjustment for known colorectal cancer risk factors (highest quartile vs. lowest: for enterodiol, odds ratio ¼ 1.11, 95% confidence interval: 0.56, 2.20 (p-trend ¼ 0.75); for enterolactone, odds ratio ¼ 1.70, 95% confidence interval: 0.88, 3.27 (p-trend ¼ 0.15)). However, sex (p-interaction ¼ 0.06) and body mass index (p-interaction <0.01) modified the relation between plasma enterolactone and colorectal cancer risk; increased risks were observed among women and subjects with a high body mass index. The association between plasma enterodiol and colorectal cancer risk was modified by smoking status; risk was increased among current smokers (p-interaction <0.01). These findings do not support the hypothesis that high plasma enterodiol or enterolactone concentrations are associated with reduced risk of colorectal cancer.
Relation between Plasma Enterodiol and Enterolactone and Dietary Intake of Lignans in a Dutch Endoscopy-Based Population
Milder, I.E.J. ; Kuijsten, A. ; Arts, I.C.W. ; Feskens, E.J.M. ; Kampman, E. ; Hollman, P.C.H. ; Veer, P. van 't - \ 2007
The Journal of Nutrition 137 (2007)5. - ISSN 0022-3166 - p. 1266 - 1271.
food frequency questionnaire - human intestinal bacteria - tandem mass-spectrometry - serum enterolactone - mammalian lignans - plant lignans - secoisolariciresinol diglucoside - liquid-chromatography - phytoestrogens - metabolism
Enterolignans are phytoestrogenic compounds derived from the conversion of dietary lignans by the intestinal microflora that may be protective against cardiovascular diseases and cancer. To evaluate the use of enterolignans as biomarkers of dietary lignan intake, we studied the relation between plasma and dietary lignans. We determined the dietary intake of 4 lignans (secoisolariciresinol (SECO), matairesinol (MAT), pinoresinol, and lariciresinol) using the European Prospective Investigation into Cancer and Nutrition FFQ, and plasma enterodiol (END) and enterolactone (ENL) concentrations were determined by liquid chromatography-tandem mass spectrometry. The population consisted of 637 men and women, aged 19-75 y, participating in a case-control study on colorectal adenomas. Participants did not use antibiotics in the preceding calendar year. We found a modest association between lignan intake and plasma END (Spearman r = 0.09, P = 0.03) and ENL (Spearman r = 0.18, P
The intake of four dietary lignans and cause specific and all-cause mortality in the Zutphen eldely study
Milder, I.E.J. ; Feskens, E.J.M. ; Arts, I.C.W. ; Bueno de Mesquita, H.B. ; Hollman, P.C.H. ; Kromhout, D. - \ 2006
European Journal of Epidemiology 21 (2006)suppl. 13. - ISSN 0393-2990 - p. 120 - 120.
Intakes of 4 dietary lignans and cause-specific and all-cause mortality in the Zutphen elderly study
Milder, I.E.J. ; Feskens, E.J.M. ; Arts, I.C.W. ; Bueno-de Mesquita, H.B. ; Hollman, P.C.H. ; Kromhout, D. - \ 2006
American Journal of Clinical Nutrition 84 (2006)2. - ISSN 0002-9165 - p. 400 - 405.
breast-cancer risk - ischemic-heart-disease - plant lignans - phytoestrogen intake - mammalian lignans - postmenopausal women - serum concentrations - enterolactone - secoisolariciresinol - lariciresinol
Plant lignans are converted to enterolignans that have antioxidant and weak estrogen-like activities, and therefore they may lower cardiovascular disease and cancer risks. OBJECTIVE: We investigated whether the intakes of 4 plant lignans (lariciresinol, pinoresinol, secoisolariciresinol, and matairesinol) were inversely associated with coronary heart disease (CHD), cardiovascular diseases (CVD), cancer, and all-cause mortality. DESIGN: The Zutphen Elderly Study is a prospective cohort study in which 570 men aged 64-84 y were followed for 15 y. We recently developed a database and used it to estimate the dietary intakes of 4 plant lignans. Lignan intake was related to mortality with the use of Cox proportional hazards analysis. RESULTS: The median total lignan intake in 1985 was 977 microg/d. Tea, vegetables, bread, coffee, fruit, and wine were the major sources of lignan. The total lignan intake was not related to mortality. However, the intake of matairesinol was inversely associated with CHD, CVD, and all-cause mortality (P
Chronic quercetin exposure affects fatty acid catabolism in rat lung
Boer, V.C.J. de; Schothorst, E.M. van; Dihal, A.A. ; Woude, H. van der; Arts, I.C.W. ; Rietjens, I.M.C.M. ; Hollman, P.C.H. ; Keijer, J. - \ 2006
Cellular and Molecular Life Sciences 63 (2006)23. - ISSN 1420-682X - p. 2847 - 2858.
dependent anion channel - diet-induced obesity - colon-cancer cells - gene-expression - dna microarray - green tea - in-vitro - polyphenols - inhibition - mice
Dietary quercetin intake is suggested to be health promoting, but this assumption is mainly based on mechanistic studies performed in vitro. Previously, we identified rat lung as a quercetin target tissue. To assess relevant in vivo health effects of quercetin, we analyzed mechanisms of effect in rat lungs of a chronic (41 weeks) 1% quercetin diet using whole genome microarrays. We show here that fatty acid catabolism pathways, like beta-oxidation and ketogenesis, are up-regulated by Dietary quercetin intake is suggested to be health promoting, but this assumption is mainly based on mechanistic studies performed in vitro. Previously, we identified rat lung as a quercetin target tissue. To assess relevant in vivo health effects of quercetin, we analyzed mechanisms of effect in rat lungs of a chronic (41 weeks) 1% quercetin diet using whole genome microarrays. We show here that fatty acid catabolism pathways, like beta-oxidation and ketogenesis, are up-regulated by the long-term quercetin intervention. Up-regulation of genes (Hmgcs2, Ech1, Acox1, Pcca, Lpl and Acaa2) was verified and confirmed by quantitative real time PCR. In addition, free fatty acid levels were decreased in rats fed the quercetin diet, confirming that quercetin affects fatty acid catabolism. This in vivo study demonstrates for the first time that fatty acid catabolism is a relevant process that is affected in rats by chronic dietary quercetin
SIRT1 stimulation by polyphenols is affected by their stability and metabolism
Boer, V.C.J. de; Goffau, L. de; Arts, I.C.W. ; Hollman, P.C.H. ; Keijer, J. - \ 2006
Mechanisms of Ageing and Development 127 (2006)7. - ISSN 0047-6374 - p. 618 - 627.
cerevisiae life-span - calorie restriction - histone deacetylase - cell-survival - transcription factors - protein deacetylases - heart-disease - flavonoids - resveratrol - quercetin
Silent information regulator two ortholog 1 (SIRT1) is the human ortholog of the yeast sir2 protein; one of the most important regulators of lifespan extension by caloric restriction in several organisms. Dietary polyphenols, abundant in vegetables, fruits, cereals, wine and tea, were reported to stimulate the deacetylase activity of recombinant SIRT1 protein and could therefore be potential regulators of aging associated processes. However, inconsistent data between effects of polyphenols on the recombinant SIRT1 and on in vivo SIRT1, led us to investigate the influence of (1) stability of polyphenols under experimental conditions and (2) metabolism of polyphenols in human HT29 cells, on stimulation of SIRT1. With an improved SIRT1 deacetylation assay we found three new polyphenolic stimulators. Epigallocatechin galate (EGCg, 1.76-fold), epicatechin galate (ECg, 1.85-fold) and myricetin (3.19-fold) stimulated SIRT1 under stabilizing conditions, whereas without stabilization, these polyphenols strongly inhibited SIRT1, probably due to H2O2 formation. Using metabolically active HT29 cells we were able to show that quercetin (a stimulator of recombinant SIRT1) could not stimulate intracellular SIRT1. The major quercetin metabolite in humans, quercetin 3-O-glucuronide, slightly inhibited the recombinant SIRT1 activity which explains the lack of stimulatory action of quercetin in HT29 cells. This study shows that the stimulation of SIRT1 is strongly affected by polyphenol stability and metabolism, therefore extrapolation of in vitro SIRT1 stimulation results to physiological effects should be done with caution.
Plasma enterolignans are associated with lower colorectal adenoma risk
Kuijsten, A. ; Arts, I.C.W. ; Hollman, P.C.H. ; Veer, P. van 't; Kampman, E. - \ 2006
Cancer Epidemiology Biomarkers and Prevention 15 (2006)6. - ISSN 1055-9965 - p. 1132 - 1136.
breast-cancer risk - serum enterolactone concentration - nested case-control - mammalian lignans - isoflavonoid phytoestrogens - circulating enterolactone - dietary phytoestrogens - flaxseed - secoisolariciresinol - enterodiol
Lignans are biphenolic compounds that occur in foods of plant origin such as whole grains, seeds, fruits and vegetables, and beverages, such as coffee and tea. Plant lignans are converted by intestinal bacteria into the enterolignans, enterodiol and enterolactone. Enterolignans possess several biological activities, whereby they may influence carcinogenesis. We studied the associations between plasma enterolignans and the risk of colorectal adenomas in a Dutch case-control study. Colorectal adenomas are considered to be precursors of colorectal cancer. Cases (n = 532) with at least one histologically confirmed colorectal adenoma and controls (n = 503) with no history of any type of adenoma were included. Plasma enterodiol and enterolactone concentrations were measured by liquid chromatography with tandem mass spectrometry. Associations were stronger for incident than for prevalent cases. When only incident cases (n = 262) were included, high compared to low plasma concentrations of enterodiol were associated with a reduction in colorectal adenoma risk after adjustment for confounding variables. Enterodiol odds ratios (95% confidence intervals) were 1.00, 0.69 (0.42-1.13), 0.60 (0.37-0.99), and 0.53 (0.32-0.88) with a significant trend (P = 0.01) through the quartiles. Although enterolactone plasma concentrations were 10-fold higher, enterolactone's reduction in risk was not statistically significant (P for trend = 0.09). Use of oral antibiotic therapy could decrease the plasma concentrations of enterolactone. Exclusion of antibiotic users resulted in similar odds ratios for both enterolignans, but the association for enterolactone became somewhat stronger (P = 0.05 versus P = 0.09). We observed a substantial reduction in colorectal adenoma risk among subjects with high plasma concentrations of enterolignans, in particular, enterodiol. These findings could be important in the prevention of colorectal adenomas
Letter to the editor: Phytoestrogens and risk of lung cancer
Hollman, P.C.H. ; Milder, I.E.J. ; Arts, I.C.W. ; Feskens, E.J.M. ; Bueno de Mesquita, H.B. ; Kromhout, D. - \ 2006
JAMA: The Journal of the American Medical Association 295 (2006)7. - ISSN 0098-7484 - p. 755 - 756.
dietary phytoestrogens - database - women - secoisolariciresinol - lariciresinol - matairesinol - pinoresinol - foods
The relative bioavailability of enterolignans in humans is enhanced by milling and crushing of flaxseed
Kuijsten, A. ; Arts, I.C.W. ; Veer, P. van 't; Hollman, P.C.H. - \ 2005
The Journal of Nutrition 135 (2005)12. - ISSN 0022-3166 - p. 2812 - 2816.
breast-cancer risk - plant lignans secoisolariciresinol - tandem mass-spectrometry - isoflavonoid excretion - serum concentrations - urinary-excretion - liquid-chromatography - postmenopausal women - plasma enterolactone - phytoestrogen intake
Flaxseed is one of the richest sources of lignans and is increasingly used in food products or as a supplement. Plant lignans can be converted by intestinal bacteria into the so-called enterolignans, enterodiol and enterolactone. For a proper evaluation of potential health effects of enterolignans, information on their bioavailability is essential. The aim of this study was to investigate whether crushing and milling of flaxseed enhances the bioavailability of enterolignans in plasma. In a randomized, crossover study, 12 healthy subjects supplemented their diet with 0.3 g whole, crushed, or ground flaxseed/(kg body weight · d). Each subject consumed flaxseed for 10 successive days separated by 11-d run-in/wash-out periods, in which the subjects consumed a diet poor in lignans. Blood samples were collected at the end of each run-in/wash-out period, and at the end of each supplement period. Plasma enterodiol and enterolactone were measured using LC-MS-MS. The mean relative bioavailability of enterolignans from whole compared with ground flaxseed was 28% (P 0.01), whereas that of crushed compared with ground flaxseed was 43% (P 0.01). Crushing and milling of flaxseed substantially improve the bioavailability of the enterolignans
Relation between plasma enterolignans and colorectal adenomas : a Dutch case-control study
Kuijsten, A. ; Arts, I.C.W. ; Hollman, P.C.H. ; Veer, P. van 't; Kampman, E. - \ 2005
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