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    '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.

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    Nutrition and cognition in older adults : studies on the role of glucose, sucrose, protein, vitamin B12 and folic acid
    Zwaluw, N.L. van der - \ 2014
    Wageningen University. Promotor(en): Lisette de Groot, co-promotor(en): Ondine van de Rest; Rosalie Dhonukshe-Rutten. - Wageningen : Wageningen University - ISBN 9789462571075 - 184
    ouderenvoeding - voeding - ouderen - kenvermogen - glucose - sucrose - eiwittoevoegingen - vitamine b12 - dementie - elderly nutrition - nutrition - elderly - cognition - glucose - sucrose - protein supplements - vitamin b12 - dementia

    The age-related cognitive decline and the increase in dementia patients are large problems in societies with growing ageing populations. No cure is present for dementia, while the available medication only focuses on alleviating symptoms. It is therefore of major importance to find risk factors that can modify the development of cognitive decline and dementia. Pre-clinical and observational studies suggest a role for nutrients. Evidence derived from randomized controlled trials (RCTs) is, however, limited and equivocal with most studies showing no effect and only a few studies showing a beneficial effect of a nutritional intervention. In the current thesis, we investigated the acute and longer-term effects of different nutrients, i.e. glucose and sucrose, protein, resistance-type exercise training with or without protein, and vitamin B12 and folic acid in order to optimize and preserve cognitive functions in non-demented elderly people.

    A comprehensive literature review was performed on the acute effects of glucose and sucrose on cognitive performance (Chapter 2). Glucose is the most important fuel for the brain, and as such, manipulation of the supply of glucose may affect cognitive functions. The main conclusion of our review was that a glucose load may have a short-term beneficial effect on episodic memory. Enhancing effects on other cognitive domains were less clear, partly due to the small number of studies examining these effects. Limited research was also done on the possible effects of sucrose on cognitive functions. Therefore, we investigated the acute effects of 50 g of glucose and 100 g of sucrose on a broad spectrum of cognitive functions reflecting performance on episodic memory, working memory, attention and information processing speed, and executive functions (Chapter 3). This was done by a cross-over study in 43 elderly participants who had self-reported memory complaints. In contrast to the conclusion of our review, we did not observe an effect of glucose or sucrose on episodic memory, though we showed a beneficial effect of sucrose on attention and information processing speed.

    Protein supplementation was the next nutritional intervention that was investigated. Several amino acids are precursors for neurotransmitters, and their supply may affect the synthesis and release of these neurotransmitters, and may consequently affect cognitive performance. A 24-week randomized placebo-controlled trial was carried out in 65 frail and pre-frail elderly people (Chapter 4). The protein supplementation included twice a day 15 grams of protein in the form of a drink. Reaction time improved more in the protein group compared to the placebo group, but the scores on the cognitive domains, i.e. episodic memory, attention and working memory, information processing speed, and executive functions, or the other single test scores, did not differ between treatment groups. In addition, we investigated the effects of 24 weeks resistance-type exercise training with and without protein supplementation in pre-frail and frail elderly people (Chapter 5). Exercise training without extra protein (n=62) improved performance on the domain attention and working memory. Exercise training together with protein supplementation (n=65) improved performance on information processing speed.

    Last, the role of vitamin B12 and folate on cognitive health was investigated. Low levels of these nutrients can increase homocysteine levels, which is a suggested risk factor for cognitive decline. The effect of daily supplementation with 500 µg vitamin B12 and 400 µg folic acid was investigated in 2,919 participants for two years (Chapter 6). Global cognitive function and episodic memory were assessed in the total study population, whereas extensive neuropsychological testing was done in a subpopulation (n=856). B-vitamin supplementation did not improve cognitive domain scores. Only a small, though significant, effect was observed on global cognitive performance, measured by the Mini-Mental State Examination, but this was suggested to be due to chance. Brain MRI scans were made in a subgroup (n=218) after two years of intervention to obtain volumetric measures of grey and white matter, and total brain volume (Chapter 7). We investigated the cross-sectional associations between follow-up levels of folate, homocysteine and three vitamin B12 status biomarkers, e.g. methylmalonic acid, holotranscobalamin and serum vitamin B12, and brain volumes. Fully adjusted regression models showed a borderline significant association between plasma homocysteine and total brain volume, with a stronger association in the group that received B-vitamin supplementation. Serum B12 and holotranscobalamin were not associated with brain volumes, whereas high methylmalonic acid levels were associated with lower brain volumes in the group that received B-vitamins. In contrast, higher folate levels were associated with lower total brain volumes. In addition, when comparing the group that received two years of B-vitamin supplementation and those who did not, we observed lower brain volumes in the B-vitamin group, which might be a result of a difference in age between the two groups.

    To conclude, the nutritional intervention studies showed little evidence for a beneficial effect on cognitive performance in relatively healthy older adults. Given the large problem of dementia, research on modifiable risk factors, including nutrition, should continue, with well thought out research methods, including large and long-term observational and intervention studies with high-sensitive study populations and early biomarkers (e.g. imaging techniques) for cognitive decline in combination with neuropsychological tests. In this way, nutrition can be added to the list of lifestyle factors that can fight dementia.

    Bones, brains and B-vitamins : the impact of vitamin B12, folate and homocysteine on bone health and cognitive function in elderly
    Wijngaarden, J.P. van - \ 2013
    Wageningen University. Promotor(en): Lisette de Groot, co-promotor(en): Rosalie Dhonukshe-Rutten. - Wageningen : Wageningen UR - ISBN 9789461737151 - 192
    botontkalking - kenvermogen - ouderen - beenderen - vitamine b12 - foliumzuur - homocysteïne - vitaminetoevoegingen - botbreuken - voedingstoestand - osteoporosis - cognition - elderly - bones - vitamin b12 - folic acid - homocysteine - vitamin supplements - bone fractures - nutritional state


    An elevated homocysteine level has been indicated as a risk factor for cardiovascular disease, cognitive decline, and fractures. Supplementation of vitamin B12 and folic acid in order to normalize homocysteine levels might be of substantial public health importance as this might reduce the risk for several age-related conditions. This thesis focuses on two health outcomes frequently associated with elevated homocysteine levels and low levels of vitamin B12 and folate: osteoporosis and cognitive decline later in life.


    Findings are presented in the context of a model which links dietary intake to biomarkers of nutritional status and subsequently to health outcomes. Two systematic reviews with meta-analyses investigated the current status of knowledge about the association of vitamin B12 intake and status with cognitive function, and the association of homocysteine, vitamin B12 and folate status with bone health. Baseline data of the B-PROOF study were used to assess 1) the association of vitamin B12 intake with status according to four biomarkers (vitamin B12, holotranscobalamin (holoTC), methylmalonic acid (MMA) and homocysteine), 2) the mutual association among these four vitamin B12 biomarkers and 3) the association between homocysteine, vitamin B12 biomarkers, folate and cognitive function. The effect of 2-year daily vitamin B12 (500 μg) and folic acid (400 μg) supplementation on fracture risk was assessed in the B-PROOF study, a large (N=2919) randomized controlled trial in elderly people (aged ≥65 years) with an elevated homocysteine level (≥12.0 µmol/L).


    The systematic review of the literature showed no or inconsistent associations of vitamin B12 intake with cognitive function. Furthermore, serum vitamin B12 was not associated with risk of dementia, global cognition or memory. Studies on MMA and holoTC reported significant associations with risk of dementia, Alzheimer’s disease and global cognition. A meta-analysis showed that serum/plasma vitamin B12 per 50 pmol/L was borderline significantly associated with a lower fracture risk (RR=0.96, 95% CI = 0.92-1.00) and that homocysteine was significantly associated with a higher fracture risk (RR=1.04, 95% CI = 1.02-1.07). Meta-analyses regarding vitamin B12, folate and homocysteine levels and BMD did not show significant associations.

    In the B-PROOF study a doubling of vitamin B12 intake was associated with 9% higher levels of vitamin B12, 15% higher holoTC, 9% lower MMA and 2% lower homocysteine, saturation of biomarkers occurs with dietary intakes of >5 μg B12. Levels of MMA and homocysteine were higher when vitamin B12 levels were below 330 pmol/L and when holoTC levels were below 100 pmol/L, with a steep elevation when levels of vitamin B12 and HoloTC were below 220 and 50 pmol/L respectively. At baseline, levels of vitamin B12 and holoTC were not associated with cognitive function in any cognitive domain. Levels of homocysteine (β= -0.009), folate (β= 0.002), MMA (β= -0.163) and the wellness score – a vitamin B12 biomarker combination score - (β= 0.048) were significantly associated with the domain of episodic memory. Additionally, homocysteine (β= -0.015) and the wellness score (β= 0.103) were significantly associated with the domain information processing speed.

    The B-PROOF intervention did not lower the risk of fracture in the total population (HR=0.84, 95% CI = 0.58-1.22). Per protocol subgroup analysis of elderly aged >80 years, showed a lower risk of fracture in the intervention group (HR=0.28, 95% CI 0.10-0.74). We observed more cancer cases in the intervention group (HR=1.55, 95% CI = 1.04-2.30) compared to the placebo group. We cannot rule out the possibility of accelerated cancer progression as a possible negative side effect.


    Our literature reviews and observational data confirm an association of levels of homocysteine, vitamin B12 and folate with cognitive function and fracture risk in elderly. Supplementation with vitamin B12 and folic acid did not lower the risk of fracture in the total study population. Though positive effects on fracture incidence emerged in elderly aged >80 years, these benefits should be weighed against potential risks.

    Approaches for setting micronutrient recommendations : a case study of vitamin B12 for adults and elderly people
    Doets, E.L. - \ 2012
    Wageningen University. Promotor(en): Pieter van 't Veer; Lisette de Groot, co-promotor(en): Adrienne Cavelaars. - S.l. : s.n. - ISBN 9789461732354 - 204
    vitamine b12 - dieetrichtlijnen - aanbevolen dagelijkse hoeveelheden - volwassenen - ouderen - europa - harmonisatie - vitamin b12 - dietary guidelines - recommended dietary allowances - adults - elderly - europe - harmonization

    Background: Most countries in Europe provide recommendations on the micronutrient composition of diets to fulfil requirements of nearly all individuals in the general apparently healthy population. However as each country uses its own methods for deriving such recommendations, there is large variation between countries in the recommended micronutrient intakes. The objectives of this thesis are to signal key issues for harmonizing approaches for establishing micronutrient recommendations for adults and elderly across Europe and to illustrate standardized and transparent review methods that can be used to summarize and evaluate the evidence-base for setting recommendations, using vitamin B12 as a case micronutrient.
    Methods: First the need for harmonization is substantiated by a descriptive study on the variation in published micronutrient recommendations across Europe. In addition methodological factors were identified that should be considered for alignment of recommended intakes across Europe. Secondly, the evidence-base for establishing recommended vitamin B12 intakes was summarized in two systematic reviews. One review focused on requirements for the compensation of daily obligatory losses (factorial approach) and the other review evaluated the relation of vitamin B12 intake and status with cognitive performance (dose-response approach). Whether interactions between folate and vitamin B12 on cognitive performance should be considered for establishing recommended vitamin B12 intakes was evaluated using data from 2203 Norwegian elderly from the Hordaland Homocysteine Study.
    Results: For harmonizing approaches for establishing micronutrient recommendations, standard methods are needed to a)-select health indicators and define adequate biomarker concentrations, b)-make assumptions about inter-individual variation in requirements, c)-derive bioavailability factors, and d)-select and interpret evidence on requirements. The first systematic review showed that daily vitamin B12 losses in apparently healthy adults and elderly probably range between 2.6-3.9 µg and bioavailability from the usual diet may range between 29 and 37% rather than the generally assumed 50%.
    Dose-response evidence from 2 randomized controlled trials and 19 prospective cohort studies showed no or inconsistent associations between vitamin B12 intake or status and dementia, Alzheimer’s Disease, global cognitive function or domain-specific cognitive function in adults and elderly people. Cross-sectional analyses in the Norwegian cohort study showed that low plasma vitamin B12 in combination with high folate was associated with better cognitive performance. However, these associations were not observed for sensitive markers of vitamin B12 status.
    Conclusion: The main conclusion of this thesis is that evidence underlying current recommended vitamin B12 intakes is old and has large uncertainties, whereas the available evidence on the relation between vitamin B12 and cognitive performance is yet not convincing and thereby limits its use as an outcome for estimating vitamin B12 requirements.
    The relation between vitamin B12 intake and markers of vitamin B12 status seems the best alternative, but sound statistical methods to define recommendations based on these dose-response data should be further developed.

    Vitamine B12, D, foliumzuur en leeftijdgerelateerde aandoeningen
    Brouwer, E.M. ; Wijngaarden, J.P. van - \ 2011
    Voeding Nu 4 (2011)13. - ISSN 1389-7608 - p. 20 - 21.
    ouderen - botbreuken - gezondheidsbescherming - ziektepreventie - vitaminen - supplementen - foliumzuur - vitamine b12 - vitamine d - deficiëntie - voeding en gezondheid - elderly - bone fractures - health protection - disease prevention - vitamins - supplements - folic acid - vitamin b12 - vitamin d - deficiency - nutrition and health
    Dat vitaminen en mineralen een positieve invloed uit kunnen oefenen op specifieke lichaamsprocessen is bekend. Twee promovendi van Wageningen Universiteit richten zich op het mogelijke verband tussen vitamine B12, foliumzuur en vitamine D en verschillende leeftijdgerelateerde aandoeningen. De associatie tussen een verhoogd homocysteïnegehalte en een verhoogd risico op fracturen was aanleiding voor een groot trial onderzoek onder ouderen. Dit B-PROOF onderzoek loopt nog.
    Dietary folate intake: is there a need for folic acid fortification in the Netherlands?
    Winkels, R.M. - \ 2008
    Wageningen University. Promotor(en): M.B. Katan, co-promotor(en): P. Verhoef; Ingeborg Brouwer. - S.l. : S.n. - ISBN 9789085852001 - 133
    foliumzuur - foliumzuurtekort - fortificatie - dieet - voedingsstoffenopname (mens en dier) - vitamine b12 - biologische beschikbaarheid - dieetrichtlijnen - nederland - geslacht (gender) - folic acid - folic acid deficiency - fortification - diet - nutrient intake - vitamin b12 - bioavailability - dietary guidelines - netherlands - gender
    Vitamin B12 synthesis in Lactobacillus reuteri
    Branco Dos Santos, F. - \ 2008
    Wageningen University. Promotor(en): Willem de Vos, co-promotor(en): J. Hugenholtz. - [S.l.] : S.n. - ISBN 9789085049906 - 2008
    vitamine b12 - lactobacillus reuteri - biosynthese - genexpressieanalyse - vitamin b12 - lactobacillus reuteri - biosynthesis - genomics
    Milde vitamine B12 deficiëntie en het cognitief functioneren van ouderen : de effectiviteit van orale supplementen
    Eussen, S.J.P.M. - \ 2006
    Wageningen University. Promotor(en): Wija van Staveren; W.H.L. Hoefnagels, co-promotor(en): Lisette de Groot. - [S.l.] : S.n. - ISBN 9789085044314 - 142
    vitamine b12 - vitaminetekorten - mentale vaardigheid - verstandelijk gehandicapt - vitaminetoevoegingen - bijvoeding - ouderen - ouderdom - kenvermogen - vitamin b12 - vitamin deficiencies - mental ability - mental retardation - vitamin supplements - supplementary feeding - elderly - old age - cognition
    Cobalamin deficiency is common in older people and has been recognised as a possible cause for several clinical manifestations such as anaemia and cognitive impairment. Markers for cobalamin deficiency include increased concentrations of plasma total homocysteine (tHcy) and methylmalonic acid (MMA), and decreased concentrations of holotranscobalamin (holoTC). Cross sectional analysis in this thesis confirmed that impaired cognitive performance was associated with relatively unfavourable concentrations of markers for cobalamin status. These results are in line with findings from previous cross-sectional and prospective studies and suggest a role for cobalamin status in cognitive function, in particular because cobalamin deficiency is highly prevalent in old age. According to our recruitment activities it appeared that 26.6% of the older people had mild cobalamin deficiency, which we defined as low to low-normal cobalamin concentrations in combination with increased MMA concentrations. Normalizing mild cobalamin deficiency, defined as a decrease of respectively 80% to 90% of the estimated maximum reduction in plasma MMA concentrations, could be achieved by supplementing daily oral doses of 647 mg to 1032 mg crystalline cobalamin. The main purpose of our research was to investigate whether daily supplementation with such a high dose of oral cobalamin alone or in combination with folic acid has beneficial effects on cognitive function in people aged 70 years or older with mild cobalamin deficiency. We did this in a double-blind, placebo-controlled trial with a relatively large number of carefully selected participants, and an extensive assessment of cognitive function. In total, 195 individuals were randomized to receive either 1,000 μg cobalamin, or 1,000 μg cobalamin + 400 μg folic acid, or placebo for 24 weeks. Markers for cobalamin status and cognitive function were assessed before and after 24 weeks of treatment. Assessment of cognitive function included the domains of attention, construction, sensomotor speed, memory and executive function. Cobalamin status did not change in the placebo group, whereas oral cobalamin supplementation corrected mild cobalamin deficiency. Improvement in one domain (memory function) was observed in all treatment groups, and was greater in the placebo group than in the group who received cobalamin alone ( P = 0.0036). Oral supplementation with cobalamin alone or in combination with folic acid for 24 weeks was not associated with improvements in other cognitive functions. Blood collection after cessation of oral cobalamin supplementation showed that adequate cobalamin status may maintain for a period of up to 5 months after cessation. Despite the null finding of this trial, recent studies provide clues for future research in improving cognitive function.
    Vitamine B12 en cognitieve functies
    Eussen, S.J.P.M. ; Groot, C.P.G.M. de; Hoefnagels, W.H.L. ; Staveren, W.A. van - \ 2004
    Voeding Nu 4 (2004)4. - ISSN 1389-7608 - p. 29 - 31.
    ouderen - vitamine b12 - vitaminetekorten - voedingsstoffentekorten - voedingstoestand - deficiëntie - cognitieve ontwikkeling - mentale vaardigheid - supplementen - toevoegingen - wetenschappelijk onderzoek - elderly - vitamin b12 - vitamin deficiencies - nutrient deficiencies - nutritional state - deficiency - cognitive development - mental ability - supplements - additives - scientific research
    Vitamine B12-deficiëntie is een relatief veel voorkomend probleem bij ouderen. Wageningen Universiteit onderzoekt wat de optimale hoeveelheid vitamine B12 in capsules zou moeten zijn om een vitamine B12-deficiëntie te behandelen en of deze hoeveelheid B12 gunstige effecten heeft op het cognitief functioneren bij ouderen met een vitamine B12-deficiëntie
    Vitamin B12: a novel indicator of bone health in vulnerable groups
    Dhonukshe-Rutten, R.A.M. - \ 2004
    Wageningen University. Promotor(en): Wija van Staveren, co-promotor(en): Lisette de Groot. - [S.I.] : S.n. - ISBN 9789085041078
    voeding - ouderen - voedselsamenstelling - vitaminen - vitamine b12 - beenderen - skelet - beendervorming - botontkalking - gezondheid - nutrition - elderly - food composition - vitamins - vitamin b12 - bones - skeleton - bone formation - osteoporosis - health

    Background: A number of modifiable predictors for osteoporosis and fractures have been identified, including nutritional factors, such as vitamin D deficiency and low calcium intake. Cobalamin deficiency has been suggested to affect bone metabolism. Pernicious anaemia, which can result in cobalamin deficiency, has been identified as a risk factor for osteoporosis. Also, it is known that homocystinuria patients are of ten diagnosed with osteoporosis. Both moderate hyperhomocysteinemia and vitamin B12 deficiency are highly prevalent in old age and may play a role in diseases characteristic for old age.
    Objectives: 1) To show the associations of vitamin B12 and homocysteine with measures of bone health in three different populations. 2) To assess the effect of supplementation with 1000 mg crystalline cobalamin, carried either by a milk product or a capsule, on cobalamin status in mildly cobalamin deficient Dutch elderly people .
    Results: Data analyses in three different populations supplied the following information. Macrobiotic-fed adolescents: adolescents (9-15 y) with a low BMD had a significantly less favorable vitamin B12 status (adjusted mean, SD: 344 :t 24 pmol/L) and MMA status (adjusted mean, P5, P95: 0.31 [0.26, 0.35] f-lIDol/L) than adolescents with a normal BMD, with levels of respectively 442 (18) and 0.20 (0.16, 0.23) f-lmol/L. Free-living elderly: An increased Hcy level appeared to be a strong and independent risk factor for osteoporotic fractures in elderly men and women of the Longitudinal Aging Study Amsterdam (n=1267, mean age: 76 yrs). Relative risks (95% CI) for the highest Hcy quartile versus lowest three homocysteine quartiles were 4.6 (1.4-14.5) in men, and 1.8 (0.8-3.7) in women. Frail elderly people: Osteoporosis (defined by BMD T-score< -2.5) occurred almost five times more of ten in frail elderly women with a marginal vitamin B12 status and seven times more of ten in women with a deficient vitamin B12 status than in women with a normal status in the VFit-study. Intervention study with vitamin B12: Crystalline cobalamin added to milk is an effective alternative for cobalamin capsules in improving cobalamin status.
    Conclusions: We found a relevant association between vitamin B12 metabolites and bone health in various studies with different study designs and diverse populations. Since these observed associations broaden the scope for randomized clinical trials, we conducted an intervention study in which we showed that milk enriched with vitamin B12 is an as effective treatment as cobalamin capsules.
    Evidence for the involvement of corrinoids and factor F430 in the reductive dechlorination of 1,2-dichloroethane by Methanosarcina barkeri.
    Holliger, C. ; Schraa, G. ; Stupperich, E. ; Stams, A.J.M. ; Zehnder, A.J.B. - \ 1992
    Journal of Bacteriology 174 (1992). - ISSN 0021-9193 - p. 4427 - 4434.
    anaërobe micro-organismen - bacteriën - ethyleendichloride - degradatie - vitamine b12 - anaerobes - bacteria - ethylene dichloride - degradation - vitamin b12
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