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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    On a collection of deep-water shrimp (Crustacea, Decapoda) from the Dutch Caribbean, with the description of a new species of Pseudocoutierea
    Olthof, Gabriël ; Becking, Leontine E. ; Fransen, Charles H.J.M. - \ 2018
    Zootaxa 4415 (2018)3. - ISSN 1175-5326 - p. 533 - 548.
    Crustacea - Decapoda - Deep reef - Dutch Caribbean - New records - New species - Pseudocoutierea
    A collection of shrimp from deep reefs in the Dutch Caribbean is described. Most material originates from the Bonaire deep reef expedition (2013) by Wageningen Marine Research of Wageningen University. Some additional material was available from dives on Curaçao (2014). A new species of Pseudocoutierea Holthuis was recognized in the material collected off Bonaire. The new species is described and illustrated and its position in the phylogeny of the genus Pseudocoutierea analyzed. A key to the species in the genus is presented.
    Hypothermic perfusion with retrograde outflow during right hepatectomy is safe and feasible
    Reiniers, Megan J. ; Olthof, Pim B. ; Golen, Rowan F. van; Heger, Michal ; Beek, Adriaan A. van; Meijer, Ben ; Leen, René ; Kuilenburg, André B.P. van; Mearadji, Banafsche ; Bennink, Roelof J. ; Verheij, Joanne ; Gulik, Thomas M. van - \ 2017
    Surgery 162 (2017)1. - ISSN 0039-6060 - p. 48 - 58.

    Background: In situ hypothermic perfusion during liver resection performed under vascular inflow occlusion decreases hepatic ischemia-reperfusion injury, but technical limitations have restricted its widespread use. In situ hypothermic perfusion with retrograde outflow circumvents these impediments and thus could extend the applicability of in situ hypothermic perfusion. The safety and feasibility of in situ hypothermic perfusion with retrograde outflow were analyzed in selected patients undergoing right (extended) hepatectomy and compared to intermittent vascular inflow occlusion, the gold standard method, in this randomized pilot study. Methods: Patients were first screened for parenchymal liver disease (exclusion criteria: steatosis ≥30%, cirrhosis, or cholestasis). Study participants were randomized intraoperatively to undergo in situ hypothermic perfusion with retrograde outflow (n = 9) or intermittent vascular inflow occlusion (n = 9). The target liver core temperature during in situ hypothermic perfusion with retrograde outflow was 28°C. The primary end point was ischemia-reperfusion injury (expressed by peak postoperative transaminase levels). Secondary outcomes included functional liver regeneration (assessed by hepatobiliary scintigraphy) and clinical outcomes. Results: Peak transaminase levels, total bilirubin, and the international normalized ratio were similar between both groups, although a trend toward more rapid normalization of bilirubin levels was noted for the in situ hypothermic perfusion with retrograde outflow group. Functional liver regeneration as evaluated by hepatobiliary scintigraphy was improved on postoperative day 3 following in situ hypothermic perfusion with retrograde outflow but not after intermittent vascular inflow occlusion. Furthermore, in situ hypothermic perfusion with retrograde outflow (requiring continuous ischemia) was comparable to intermittent vascular inflow occlusion for all clinical outcomes, including postoperative complications and hospital stay. Conclusion: The use of in situ hypothermic perfusion with retrograde outflow appears to be safe and feasible in selected patients with healthy liver parenchyma and may benefit early functional liver regeneration. Future applications of in situ hypothermic perfusion with retrograde outflow include patients with damaged liver parenchyma who would require major hepatic resection with a prolonged vascular inflow occlusion duration.

    Warm ischemia time-dependent variation in liver damage, inflammation, and function in hepatic ischemia/reperfusion injury
    Olthof, Pim B. ; Golen, Rowan F. van; Meijer, Ben ; Beek, Adriaan A. van; Bennink, Roelof J. ; Verheij, Joanne ; Gulik, Thomas M. van; Heger, Michal - \ 2017
    Biochimica et Biophysica Acta. Molecular Basis of Disease 1863 (2017)2. - ISSN 0925-4439 - p. 375 - 385.

    Background Hepatic ischemia/reperfusion (I/R) injury is characterized by hepatocellular damage, sterile inflammation, and compromised postoperative liver function. Generally used mouse I/R models are too severe and poorly reflect the clinical injury profile. The aim was to establish a mouse I/R model with better translatability using hepatocellular injury, liver function, and innate immune parameters as endpoints. Methods Mice (C57Bl/6J) were subjected to sham surgery, 30 min, or 60 min of partial hepatic ischemia. Liver function was measured after 24 h using intravital microscopy and spectroscopy. Innate immune activity was assessed at 6 and 24 h of reperfusion using mRNA and cytokine arrays. Liver inflammation and function were profiled in two patient cohorts subjected to I/R during liver resection to validate the preclinical results. Results In mice, plasma ALT levels and the degree of hepatic necrosis were strongly correlated. Liver function was bound by a narrow damage threshold and was severely impaired following 60 min of ischemia. Severe ischemia (60 min) evoked a neutrophil-dominant immune response, whereas mild ischemia (30 min) triggered a monocyte-driven response. Clinical liver I/R did not compromise liver function and displayed a cytokine profile similar to the mild I/R injury model. Conclusions Mouse models using ≤ 30 min of ischemia best reflect the clinical liver I/R injury profile in terms of liver function dynamics and type of immune response. General significance This short duration of ischemia therefore has most translational value and should be used to increase the prospects of developing effective interventions for hepatic I/R.

    Connecting care, sport and physical activity. Study design to evaluate the effect of the role of neighbourhood sport coaches.
    Molleman, G. ; Wagemakers, A. ; Smit, E. ; Leenaars, K.E.F. ; Preller, L. ; Bloten, H. ; Olthof, S. ; Koelen, M. ; Velden, J. van der - \ 2013
    Evaluation design to study the role of neighbourhood sport coaches in connecting primary care, sport and physical activity
    Wagemakers, M.A.E. ; Molleman, G. ; Leenaars, K.E.F. ; Smit, E. ; Preller, L. ; Bloten, H. ; Olthof, S. ; Velden, J. van der; Koelen, M. - \ 2013
    In: 9th Annual Meeting and 4th Conference of HEPA Europe, 21-24 October 2013, Helsinki, Finland. - Helsinki : Keuruskopio Oy - p. 72 - 72.
    The metropolitan park: searching for a new typology for intermediate green areas in urban fields
    Brinkhuijsen, M. ; Velde, R. van der; Graaf, E. de; Kruit, E. ; Lodder, A. - \ 2011
    Ongoing urbanization in metropolitan regions creates a wish for large green areas in the urban peripheries for recreational purposes. Agricultural landscapes are being replaced with woods, nature and water to provide citizens with space for outdoor recreation and other activities. Park-like settings and facilities are being mingled with rational agricultural landscape images. These large areas – up to 1500 hectares – are supposed to provide common recreation for adjacent residential areas, but their size justifies higher ambitions. They are meant to perform as an outstanding regional attraction, and, furthermore, to meet other demands such as climate adaption, water management, nature and agricultural production. They should be ’metropolitan parks’ at a regional level, which asks for a clear identity and a set of appealing, distinctive facilities. While in the past decades public authorities used to purchase, construct and maintain areas like these, nowadays the involvement of private partners is essential for the realization and subsistence of large green areas. These developments result in new design challenges. Well-known design strategies, concepts, images and programs for urban parks don’t suffice and are subject for debate. This paper will present the results of studies and debates initiated by the Dutch Association for Landscape Architecture NVTL in 2010 in order to light up the design of large parks in urban agglomerations. Plans for five large ’metropolitan’ parks in the Netherlands will be compared: Park 21 Haarlemmermeer (design by Vista Landscape Architecture and Urban Planning), Landschapspark Buytenland Rotterdam (design by PVLA), Amstelscheg Amsterdam (design by ?), Park Lingezegen Arnhem-Nijmegen (master plan by Feddes Olthof Landscape Architects) and Park Leidsche Rijn Utrecht (design by West 8 landscape architects). The characteristics and challenges of these areas are similar: their hybrid character, being both park and landscape; the multiple recreational purposes from neighbourhood park to regional attraction; the combination of recreational and other land uses; the diversity of stakeholders; the uncertainties by reason of the extended development time. There is the problem of the need for coherence in an area which is way too large and complex to be wrapped up in a few images. Despite the similar problems, the design concepts and strategies are diverse. The question is if the solutions brought up by the designers will ensure attractive future environments and if they offer innovative concepts for intermediate green areas in metropolitan networks.
    Gewaspatronen H-WodKa: Studie Atlas
    Olthof, W. ; Gun, J. van der; Kooistra, L. - \ 2011
    Wageningen : Wageningen University (Deelrapport project PSPM op de kaart ) - 18
    akkerbouw - gewassen - opbrengsten - precisielandbouw - monitoring - zuidhollandse eilanden - arable farming - crops - yields - precision agriculture - monitoring - zuidhollandse eilanden
    Deze atlas bevat kaarten met gewaspatronen voor 10 agrarische percelen in de Hoeksche Waard voor de periode 2006-2010. De kaarten geven een indicatie van de biomassa voor drie momenten in een groeiseizoen (twee in 2010). Deze momenten betreffen het begin, het midden en het eind van het groeiseizoen. De timing van de opnames is afhankelijk van de beschikbaarheid van geschikte remote sensing beelden.
    Prospective study on dietary intakes of folate, betaine, and choline and cardiovascular disease risk in women
    Dalmeijer, G.W. ; Olthof, M.R. ; Verhoef, P. ; Bots, M.L. ; Schouw, Y.T. van der - \ 2008
    European Journal of Clinical Nutrition 62 (2008). - ISSN 0954-3007 - p. 386 - 394.
    plasma homocysteine concentrations - food-frequency questionnaire - ischemic-heart-disease - folic-acid - vascular-disease - healthy-men - myocardial-infarction - relative validity - stroke - vitamin-b-6
    Objective: To investigate the association between dietary intakes of folate, betaine and choline and the risk of cardiovascular disease (CVD). Design: Prospective cohort study. Subjects: A total of 16 165 women aged 49¿70 years without prior CVD. Subjects were breast cancer screening participants in the PROSPECT¿EPIC cohort, which is 1 of the 2 Dutch contributions to the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: Each participant completed a validated food frequency questionnaire. Folate intake was calculated with the Dutch National Food Database. Betaine and choline intakes were calculated with the USDA database containing choline and betaine contents of common US foods. Data on coronary heart disease (CHD) events and cerebrovascular accident (CVA) events morbidity data were obtained from the Dutch Centre for Health Care Information. Results: During a median follow-up period of 97 months, 717 women were diagnosed with CVD. After adjustment, neither folate, nor betaine, nor choline intakes were associated with CVD (hazard ratios for highest versus lowest quartile were 1.23 (95% confidence interval 0.75; 2.01), 0.90 (0.69; 1.17), 1.04 (0.71; 1.53), respectively). In a subsample of the population, high folate and choline intakes were statistically significantly associated with lower homocysteine levels. High betaine intake was associated with slightly lower high-density lipoprotein (HDL)-cholesterol concentrations. Conclusion: Regular dietary intakes of folate, betaine and choline were not associated with CVD risk in post-menopausal Dutch women. However, the effect of doses of betaine and choline beyond regular dietary intake ¿ for example, via supplementation or fortification ¿ remains unknown.
    Effect of folic acid and betaine supplementation on flow-mediated dilation: A randomized, controlled study in healthy volunteers
    Olthof, M.R. ; Bots, M.L. ; Katan, M.B. ; Verhoef, P. - \ 2006
    PloS Clinical trials 1 (2006)2. - ISSN 1555-5887
    Objectives We investigated whether lowering of fasting homocysteine concentrations, either with folic acid or with betaine supplementation, differentially affects vascular function, a surrogate marker for risk of cardiovascular disease, in healthy volunteers. As yet, it remains uncertain whether a high concentration of homocysteine itself or whether a low folate status¿its main determinant¿is involved in the pathogenesis of cardiovascular disease. To shed light on this issue, we performed this study. Design This was a randomized, placebo-controlled, double-blind, crossover study. Setting The study was performed at Wageningen University in Wageningen, the Netherlands. Participants Participants were 39 apparently healthy men and women, aged 50¿70 y. Interventions Participants ingested 0.8 mg/d of folic acid, 6 g/d of betaine, and placebo for 6 wk each, with 6-wk washout in between. Outcome Measures At the end of each supplementation period, plasma homocysteine concentrations and flow-mediated dilation (FMD) of the brachial artery were measured in duplicate. Results Folic acid supplementation lowered fasting homocysteine by 20% (¿2.0 ¿mol/l, 95% confidence interval [CI]: ¿2.3; ¿1.6), and betaine supplementation lowered fasting plasma homocysteine by 12% (¿1.2 ¿mol/l; ¿1.6; ¿0.8) relative to placebo. Mean (± SD) FMD after placebo supplementation was 2.8 (± 1.8) FMD%. Supplementation with betaine or folic acid did not affect FMD relative to placebo; differences relative to placebo were ¿0.4 FMD% (95%CI, ¿1.2; 0.4) and ¿0.1 FMD% (¿0.9; 0.7), respectively. Conclusions Folic acid and betaine supplementation both did not improve vascular function in healthy volunteers, despite evident homocysteine lowering. This is in agreement with other studies in healthy participants, the majority of which also fail to find improved vascular function upon folic acid treatment. However, homocysteine or folate might of course affect cardiovascular disease risk through other mechanisms.
    Acute effect of folic acid, betaine, and serine supplements on flow-mediated dilation after methionine loading: A randomized trial
    Olthof, M.R. ; Bots, M.L. ; Katan, M.B. ; Verhoef, P. - \ 2006
    PloS Clinical trials 1 (2006)1. - ISSN 1555-5887
    coronary-artery-disease - vascular endothelial dysfunction - homocysteine-lowering therapy - placebo-controlled trial - ischemic-heart-disease - healthy-human subjects - saturated fatty-acids - plasma homocysteine - dependent vasodilation - cardiovascular events
    Objectives: We investigated whether reducing post-methionine homocysteine concentrations via various treatments other than folic acid affects vascular function, as measured through flow-mediated dilation (FMD) of the brachial artery. High fasting and post-methionine homocysteine concentrations are associated with cardiovascular disease risk, but homocysteine might be a surrogate marker for low folate status. Design: This was a randomized, placebo-controlled, double-blind, crossover study. Setting: The study took place at Wageningen University in Wageningen in the Netherlands. Participants: Participants were 39 apparently healthy men and women, aged 50 - 70 y. Interventions: Participants ingested 10 mg of folic acid, 3 g of betaine, 5 g of serine, and placebo together with an oral methionine load. Each supplement was tested on two different days. Outcome Measures: On each of the eight treatment days, plasma homocysteine concentrations and FMD were measured before ( t = 0 h, fasting) and 6 h ( t = 6 h) after methionine loading. Results: The mean (+/- SD) fasting homocysteine concentrations averaged over the eight test days were 9.6 +/- 62.1 mu mol/l. Mean fasting FMD was 3.1 +/- 2.4 FMD%. A methionine load with placebo increased homocysteine concentrations by 17.2 +/- 9.3 mu mol/l at 6 h after loading, similar to the increase following methionine loading with folic acid. A methionine load together with betaine and with serine increased homocysteine by 10.4 +/- 2.8 mu mol/l ( p<0.001 relative to placebo) and by 12.1 +/- 8.2 mu mol/l ( p<0.001 relative to placebo), respectively. Methionine loading with placebo did not affect FMD, and neither did methionine loading with folic acid, betaine, or serine; differences relative to placebo were +0.7 FMD% (95% CI, - 0.6; 1.9), +0.2 FMD% (- 1.0; 1.3), and +0.3 FMD% ( - 0.8; 1.4), respectively. Conclusions: Experimentally induced acute changes in homocysteine concentrations did not affect FMD in healthy volunteers. This implies that potential adverse effects of high homocysteine concentrations on the cardiovascular system are not mediated through vascular function. However, homocysteine or folate may affect cardiovascular disease risk through other mechanisms.
    Betaine concentration as a determinant of fasting total homocysteine concentrations and the effect of folic acid supplementation on betaine concentrations
    Boonstra, A. ; Holm, P.I. ; Ueland, P.M. ; Olthof, M.R. ; Clarke, R. ; Verhoef, P. - \ 2005
    American Journal of Clinical Nutrition 81 (2005)6. - ISSN 0002-9165 - p. 1378 - 1382.
    liver folate content - plasma homocysteine - choline deficiency - randomized-trials - healthy-men - serum - risk - homocystinuria - metaanalysis - disease
    Background: Remethylation of homocysteine to methionine can occur through either the folate-dependent methionine synthase pathway or the betaine-dependent betaine-homocysteine methyltransferase pathway. The relevance of betaine as a determinant of fasting total homocysteine (tHcy) is not known, nor is it known how the 2 remethylation pathways are interrelated. Objective: The objectives of the study were to examine the relation between plasma betaine concentration and fasting plasma tHcy concentrations and to assess the effect of folic acid supplementation on betaine concentrations in healthy subjects. Design: A double-blind randomized trial of 6 incremental daily doses of folic acid (50¿800 µg/d) or placebo was carried out in 308 Dutch men and postmenopausal women (aged 50¿75 y). Fasted blood concentrations of tHcy, betaine, choline, dimethylglycine, and folate were measured at baseline and after 12 wk of vitamin supplementation. Results: Concentrations of tHcy were inversely related to the betaine concentration (r = ¿0.17, P <0.01), and the association was independent of age, sex, and serum concentrations of folate, creatinine, and cobalamin. Folic acid supplementation increased betaine concentration in a dose-dependent manner (P for trend = 0.018); the maximum increase (15%) was obtained at daily doses of 400¿800 µg/d. Conclusions: The plasma betaine concentration is a significant determinant of fasting tHcy concentrations in healthy humans. Folic acid supplementation increases the betaine concentration, which indicates that the 2 remethylation pathways are interrelated
    A high-protein diet increases postprandial but not fasting plasma total homocysteine concentrations: a dietary controlled, crossover trial in healthy volunteers
    Verhoef, P. ; Vliet, T. van; Olthof, M.R. ; Katan, M.B. - \ 2005
    American Journal of Clinical Nutrition 82 (2005)3. - ISSN 0002-9165 - p. 553 - 558.
    vascular endothelial dysfunction - randomized controlled-trial - myocardial-infarction - methionine intake - heart-disease - fatty-acids - serum - risk - metaanalysis - men
    Background: A high plasma concentration of total homocysteine (tHcy) is associated with increased risk of cardiovascular disease. A high protein intake and hence a high intake of methionine¿the sole dietary precursor of homocysteine¿may raise plasma tHcy concentrations. Objectives: We studied whether high intake of protein increases plasma concentrations of tHcy in the fasting state and throughout the day. Design: We conducted a randomized, dietary controlled, crossover trial in 20 healthy men aged 18¿44 y. For 8 d, men consumed a controlled low-protein diet enriched with either a protein supplement [high-protein diet (21% of energy as protein)] or an isocaloric amount of short-chain glucose polymers [low-protein diet (9% of energy as protein)]. After a 13-d washout period, treatments were reversed. On days 1 and 8 of each treatment period, blood was sampled before breakfast (fasting) and throughout the day. Results: Fasting tHcy concentrations did not differ significantly after the 1-wk high-protein and the 1-wk low-protein diets. The high-protein diet resulted in a significantly higher area under the 24-h homocysteine-by-time curves compared with the low-protein diet, both on day 1 (difference: 45.1 h · µmol/L; 95% CI: 35.3, 54.8 h · µmol/L; P <0.0001) and on day 8 (difference: 24.7 h · µmol/L; 95% CI: 15.0, 34.5 h · µmol/L; P <0.0001). Conclusions: A high-protein diet increases tHcy concentrations throughout the day but does not increase fasting tHcy concentrations. As previously shown, the extent of the tHcy increase is modified by the amino acid composition of the protein diet. The clinical relevance of this finding depends on whether high concentrations of tHcy¿particularly postprandially¿cause cardiovascular disease
    Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men
    Olthof, M.R. ; Brink, E.J. ; Katan, M.B. ; Verhoef, P. - \ 2005
    American Journal of Clinical Nutrition 82 (2005)1. - ISSN 0002-9165 - p. 111 - 117.
    phosphatidylethanolamine n-methyltransferase - methotrexate treatment - rat-liver - parenteral-nutrition - vascular-disease - dna methylation - folic-acid - deficiency - betaine - folate
    Background: A high homocysteine concentration is a potential risk factor for cardiovascular disease that can be reduced through betaine supplementation. Choline is the precursor for betaine, but the effects of choline supplementation on plasma total homocysteine (tHcy) concentrations in healthy humans are unknown. Objective: The objective was to investigate whether supplementation with phosphatidylcholine, the form in which choline occurs in foods, reduces fasting and postmethionine-loading concentrations of plasma tHcy in healthy men with mildly elevated plasma tHcy concentrations. Design: In a crossover study, 26 men ingested 2.6 g choline/d (as phosphatidylcholine) or a placebo oil mixture for 2 wk in random order. Fatty acid composition and fat content were similar for both treatments. A methionine-loading test was performed on the first and last days of each supplementation period. Results: Phosphatidylcholine supplementation for 2 wk decreased mean fasting plasma tHcy by 18% (¿3.0 µmol/L; 95% CI: ¿3.9, ¿2.1 µmol/L). On the first day of supplementation, a single dose of phosphatidylcholine containing 1.5 g choline reduced the postmethionine-loading increase in tHcy by 15% (¿4.8 µmol/L; 95% CI: ¿6.8, ¿2.8 µmol/L). Phosphatidylcholine supplementation for 2 wk reduced the postmethionine-loading increase in tHcy by 29% (¿9.2 µmol/L; 95% CI: ¿11.3, ¿7.2 µmol/L). All changes were relative to placebo. Conclusions: A high daily dose of choline, supplemented as phosphatidylcholine, lowers fasting as well as postmethionine-loading plasma tHcy concentrations in healthy men with mildly elevated tHcy concentrations. If high homocysteine concentrations indeed cause cardiovascular disease, choline intake may reduce cardiovascular disease risk in humans
    Effects of Betaine Intake on Plasma Homocysteine Concentrations and Consequences for Health
    Olthof, M.R. ; Verhoef, P. - \ 2005
    Current Drug Metabolism 6 (2005)1. - ISSN 1389-2002 - p. 15 - 22.
    coronary-heart-disease - folic-acid - vascular-disease - hemodialysis-patients - n-methyltransferase - synthase deficiency - folate-deficiency - randomized-trials - risk factor - choline
    High plasma concentrations of homocysteine may increase risk of cardiovascular disease. Folic acid lowers plasma homocysteine by 25% maximally, because 5-methyltetrahydrofolate is a methyl donor in the remethylation of homocysteine to methionine. Betaine (trimethylglycine) is also a methyl donor in homocysteine remethylation, but effects on homocysteine have been less thoroughly investigated. Betaine in high doses (6 g/d and higher) is used as homocysteine-lowering therapy for people with hyperhomocysteinemia due to inborn errors in the homocysteine metabolism. Betaine intake from foods is estimated at 0.5-2 g/d. Betaine can also be synthesized endogenously from its precursor choline. Studies in healthy volunteers with plasma homocysteine concentrations in the normal range show that betaine supplementation lowers plasma fasting homocysteine dose-dependently to up to 20% for a dose of 6 g/d of betaine. Moreover, betaine acutely reduces the increase in homocysteine after methionine loading by up to 50%, whereas folic acid has no effect. Betaine doses in the range of dietary intake also lower homocysteine. This implies that betaine can be an important food component that attenuates homocysteine rises after meals. If homocysteine plays a causal role in the development of cardiovascular disease, a diet rich in betaine or choline might benefit cardiovascular health through its homocysteine-lowering effects. However betaine and choline may adversely affect serum lipid concentrations, which can of course increase risk of cardiovascular disease. However, whether the potential beneficial health effects of betaine and choline outweigh the possible adverse effects on serum lipids is as yet unclear
    Effect of Homocysteine-Lowering Nutrients on Blood Lipids: Result from Four Randomised, Placebo-Controlled Studies in Healthy Humans
    Olthof, M.R. ; Vliet, T. van; Verhoef, P. ; Zock, P.L. ; Katan, M.B. - \ 2005
    PLOS Medicine 2 (2005)5. - ISSN 1549-1676
    coronary-heart-disease - density-lipoprotein cholesterol - folic-acid supplementation - plasma homocysteine - myocardial-infarction - s-methyltransferase - controlled-trial - betaine - choline - dietary
    Background Betaine (trimethylglycine) lowers plasma homocysteine, a possible risk factor for cardiovascular disease. However, studies in renal patients and in obese individuals who are on a weight-loss diet suggest that betaine supplementation raises blood cholesterol; data in healthy individuals are lacking. Such an effect on cholesterol would counteract any favourable effect on homocysteine. We therefore investigated the effect of betaine, of its precursor choline in the form of phosphatidylcholine, and of the classical homocysteine-lowering vitamin folic acid on blood lipid concentrations in healthy humans. Methods and Findings We measured blood lipids in four placebo-controlled, randomised intervention studies that examined the effect of betaine (three studies, n = 151), folic acid (two studies, n = 75), and phosphatidylcholine (one study, n = 26) on plasma homocysteine concentrations. We combined blood lipid data from the individual studies and calculated a weighted mean change in blood lipid concentrations relative to placebo. Betaine supplementation (6 g/d) for 6 wk increased blood LDL cholesterol concentrations by 0.36 mmol/l (95% confidence interval: 0.25¿0.46), and triacylglycerol concentrations by 0.14 mmol/l (0.04¿0.23) relative to placebo. The ratio of total to HDL cholesterol increased by 0.23 (0.14¿0.32). Concentrations of HDL cholesterol were not affected. Doses of betaine lower than 6 g/d also raised LDL cholesterol, but these changes were not statistically significant. Further, the effect of betaine on LDL cholesterol was already evident after 2 wk of intervention. Phosphatidylcholine supplementation (providing approximately 2.6 g/d of choline) for 2 wk increased triacylglycerol concentrations by 0.14 mmol/l (0.06¿0.21), but did not affect cholesterol concentrations. Folic acid supplementation (0.8 mg/d) had no effect on lipid concentrations. Conclusions Betaine supplementation increased blood LDL cholesterol and triacylglycerol concentrations in healthy humans, which agrees with the limited previous data. The adverse effects on blood lipids may undo the potential benefits for cardiovascular health of betaine supplementation through homocysteine lowering. In our study phosphatidylcholine supplementation slightly increased triacylglycerol concentrations in healthy humans. Previous studies of phosphatidylcholine and blood lipids showed no clear effect. Thus the effect of phosphatidylcholine supplementation on blood lipids remains inconclusive, but is probably not large. Folic acid supplementation does not seem to affect blood lipids and therefore remains the preferred treatment for lowering of blood homocysteine concentrations
    Dietary lipids and vascular function: UK Food Standards Agency workshop report
    Sanderson, P. ; Olthof, M.R. ; Roos, N.M. de - \ 2004
    The British journal of nutrition 91 (2004)3. - ISSN 0007-1145 - p. 491 - 500.
    The UK Food Standards Agency convened a group of expert scientists to review current research investigating the effect of dietary lipids on vascular function. The workshop highlighted the need for intervention studies to be sufficiently powered for these measures and that they should be corroborated with other, more validated, risk factors for CVD. Work presented at the workshop suggested a beneficial effect of long-chain n-3 PUFA and a detrimental effect of trans fatty acids. The workshop also considered the importance of the choice of study population in dietary intervention studies and that "at risk" subgroups within the general population may be more appropriate than subjects that are unrepresentatively healthy
    Dietary serine and cystine attenuate the homocysteine-raising effect of dietary methionine: a randomized, crossover trial in humans.
    Verhoef, P. ; Steenge, G.R. ; Boelsma, E. ; Vliet, T. van; Olthof, M.R. ; Katan, M.B. - \ 2004
    American Journal of Clinical Nutrition 80 (2004)3. - ISSN 0002-9165 - p. 674 - 679.
    vascular endothelial dysfunction - plasma homocysteine - n-acetylcysteine - cardiovascular risk - heart-disease - metabolism - cysteine - blood - rats - metaanalysis
    Background: A high plasma total homocysteine (tHcy) concentration is a risk factor for cardiovascular disease. The increase in tHcy induced by methionine, the sole dietary precursor of homocysteine, might be modulated by other amino acids present in dietary proteins. Objectives: Our objectives were to compare the postprandial effect of free and dietary methionine on plasma tHcy concentrations and to investigate whether serine and cystine modify the effect of free methionine on tHcy. Design: We conducted a randomized crossover trial in 24 healthy men. Each subject ingested 4 meals on separate days, which were separated by 1 wk. tHcy concentrations were measured in the fasting state and at 2, 4, 6, 8, 10, and 24 h after meal ingestion. The meals were 1) a low-protein meal fortified with 30 mg methionine/kg body wt (reference, denoted by "Met"), 2) meal I additionally fortified with 60.6 mg serine/kg body wt (MetSer), 3) meal I additionally fortified with 12.3 mg cystine/kg body wt (MetCys), and 4) a protein-rich meal containing 30 mg methionine, 60.6 mg serine, and 12.3 mg cystine per kg body wt (Protein). Results: The mean (SD) fasting tHcy concentration was 9.1 +/- 2.7 mumol/L. Mean peak tHcy concentrations were 17.9 +/- 4.5, 14.3 +/- 3.3, 14.8 +/- 3.9, and 11.2 +/- 3.1 mumol/L after Met, MetSer, MetCys, and Protein, respectively. Compared with the mean 24-h area under the tHcy-by-time curve after Met, the mean curves after MetSer, MetCys, and Protein were 37%, 32%, and 77% smaller, respectively (all P <0.0005). Conclusions: Dietary methionine increases tHcy much less than does free methionine. Serine and cystine attenuate the tHcy-raising effect of free methionine. Thus, dietary proteins with a high content of serine or cystine relative to methionine may lead to lower postprandial tHcy responses.
    Natuur kun je ontwerpen
    Brinkhuijsen, M. ; Olthof, B. ; Pohl, N. ; Kroon, H.J.J. - \ 2003
    In: Wie is bang voor de stad? Essays over ruimtelijke ordening, natuur en verstedelijking / Woestenburg, M., Buijs, A.E., Timmermans, W, Wageningen : Blauwdruk - ISBN 9789075271102 - p. 90 - 95.
    landschapsarchitectuur - landschap - ontwerp - ecologie - natuur - cultuurlandschap - landscape architecture - landscape - ecology - design - nature - cultural landscape
    De auteurs voorspellen voor ontwerpers in de 21e eeuw nieuwe ontwerpuitdagingen en voor ecologen nieuwe onderzoeksvragen. Voor tuin- en parkarchitecten ligt er de opgave zich te verdiepen in de mogelijkheid om de ecologische betekenis van een tuin of park te verstevigen en de biodiversiteit in samenhang met met menselijke activiteiten te verhogen
    Dietary serine and cystine diminish the homocysteine raising effect of methionine in humans
    Verhoef, P. ; Steenge, G.R.S. ; Boelsma, E. ; Vliet, T. van; Olthof, M.R. ; Katan, M.B. - \ 2003
    In: Proceedings of the Fourth International Conference on Homocysteine Metabolism. - Basel, Switzerland : - p. 15 - 15.
    Effect of betaine on plasma homocysteine: a dose-response study in healthy volunteers
    Olthof, M.R. ; Vliet, T. van; Boelsma, E. ; Verhoef, P. - \ 2003
    In: Proceedings of the Fourth International Conference on Homocysteine Metabolism. - Basel : - p. 12 - 12.
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