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Folate and epigenetics : Why we should not forget bacterial biosynthesis
Kok, Dieuwertje E. ; Steegenga, Wilma T. ; McKay, Jill A. - \ 2018
- p. 1147 - 1150.
biosynthesis - DNA methylation - epigenetics - folate - intestinal bacteria - microbiota - one-carbon metabolism
Effect of vitamin B12 and folic acid supplementation on bone mineral density and quantitative ultrasound parameters in older people with an elevated plasma homocysteine level: B-PROOF, a randomized controlled trial
Enneman, A.W. ; Swart, K.M.A. ; Wijngaarden, J.P. van; Dijk, S.C. van; Ham, A.C. ; Brouwer-Brolsma, E.M. ; Zwaluw, N.L. van der; Dhonukshe-Rutten, R.A.M. ; Cammen, T.J.M. van der; Groot, C.P.G.M. de; Meurs, J.B.J. van; Lips, P. ; Uitterlinden, A.G. ; Zillikens, M.C. ; Schoor, N.M. van; Velde, N. van der - \ 2015
Calcified Tissue International 96 (2015)5. - ISSN 0171-967X - p. 401 - 409.
placebo-controlled trial - postmenopausal women - fracture risk - turnover markers - elderly-women - metaanalysis - association - population - folate - bmd
High plasma homocysteine (Hcy) levels are associated with increased osteoporotic fracture incidence. However, the mechanism remains unclear. We investigated the effect of Hcy-lowering vitamin B12 and folic acid treatment on bone mineral density (BMD) and calcaneal quantitative ultrasound (QUS) parameters. This randomized, double-blind, placebo-controlled trial included participants aged =65 years with plasma Hcy levels between 12 and 50 µmol/L. The intervention comprised 2-year supplementation with either a combination of 500 µg B12, 400 µg folic acid, and 600 IU vitamin D or placebo with 600 IU vitamin D only. In total, 1111 participants underwent repeated dual-energy X-ray assessment and 1165 participants underwent QUS. Femoral neck (FN) BMD, lumbar spine (LS) BMD, calcaneal broadband ultrasound attenuation (BUA), and calcaneal speed of sound (SOS) were assessed. After 2 years, FN-BMD and BUA had significantly decreased, while LS-BMD significantly increased (all p <0.01) and SOS did not change in either treatment arm. No statistically significant differences between the intervention and placebo group were present for FN-BMD (p = 0.24), LS-BMD (p = 0.16), SOS (p = 0.67), and BUA (p = 0.96). However, exploratory subgroup analyses revealed a small positive effect of the intervention on BUA at follow-up among compliant persons >80 years (estimated marginal mean 64.4 dB/MHz for the intervention group and 61.0 dB/MHz for the placebo group, p = 0.04 for difference). In conclusion, this study showed no overall effect of treatment with vitamin B12 and folic acid on BMD or QUS parameters in elderly, mildly hyperhomocysteinemic persons, but suggests a small beneficial effect on BUA in persons >80 years who were compliant in taking the supplement.
Results of 2-year vitamin B treatment on cognitive performance
Zwaluw, N.L. van der; Dhonukshe-Rutten, R.A.M. ; Wijngaarden, J.P. van; Brouwer, E.M. ; Rest, O. van de; Veld, P.H. in 't; Enneman, A.W. ; Dijk, S.C. van; Ham, A.C. ; Swart, K.M.A. ; Velde, N. van der; Schoor, N.M. van; Cammen, T.J.M. van der; Uitterlinden, A.G. ; Lips, P. ; Kessels, R.P.C. ; Groot, C.P.G.M. de - \ 2014
Neurology 83 (2014)23. - ISSN 0028-3878 - p. 2158 - 2166.
folic-acid supplementation - randomized controlled-trial - placebo-controlled trial - alzheimers-disease - elderly-patients - double-blind - homocysteine - metaanalysis - impairment - folate
Objective: We investigated the effects of 2-year folic acid and vitamin B12 supplementation on cognitive performance in elderly people with elevated homocysteine (Hcy) levels. Methods: This multicenter, double-blind, randomized, placebo-controlled trial included 2,919 elderly participants (65 years and older) with Hcy levels between 12 and 50 µmol/L. Participants received daily either a tablet with 400 µg folic acid and 500 µg vitamin B12 (B-vitamin group) or a placebo tablet. Both tablets contained 15 µg vitamin D3. Data were available for global cognitive functioning assessed by Mini-Mental State Examination (n = 2,556), episodic memory (n = 2,467), attention and working memory (n = 759), information processing speed (n = 731), and executive function (n = 721). Results: Mean age was 74.1 (SD 6.5) years. Hcy concentrations decreased 5.0 (95% confidence interval -5.3 to -4.7) µmol/L in the B-vitamin group and 1.3 (-1.6 to -0.9) µmol/L in the placebo group. Cognitive domain scores did not differ over time between the 2 groups, as determined by analysis of covariance. Mini-Mental State Examination score decreased with 0.1 (-0.2 to 0.0) in the B-vitamin group and 0.3 (-0.4 to -0.2) in the placebo group (p = 0.05), as determined by an independent t test. Conclusions: Two-year folic acid and vitamin B12 supplementation did not beneficially affect performance on 4 cognitive domains in elderly people with elevated Hcy levels. It may slightly slow the rate of decline of global cognition, but the reported small difference may be attributable to chance. Classification of evidence: This study provides Class I evidence that 2-year supplementation with folic acid and vitamin B12 in hyperhomocysteinemic elderly people does not affect cognitive performance.
Effect of daily vitamin B-12 and folic acid supplementation on fracture incidence in elderly individuals with an elevated plasma homocysteine concentration: B-PROOF, a randomized controlled trial
Wijngaarden, J.P. van; Swart, K.M.A. ; Enneman, A.W. ; Dhonukshe-Rutten, R.A.M. ; Dijk, S.C. van; Ham, A.C. ; Brouwer, E.M. ; Zwaluw, N.L. van der; Sohl, E. ; Meurs, J.B.J. van; Zillikens, M.C. ; Schoor, N.M. van; Velde, N. van der; Brug, J. ; Uitterlinden, A.G. ; Lips, P. ; Groot, C.P.G.M. de - \ 2014
American Journal of Clinical Nutrition 100 (2014)6. - ISSN 0002-9165 - p. 1578 - 1586.
hip fracture - osteoporotic fractures - bone turnover - d deficiency - risk - metaanalysis - folate - level - women
Background: Elevated plasma homocysteine concentrations are a risk factor for osteoporotic fractures. Lowering homocysteine with combined vitamin B-12 and folic acid supplementation may reduce fracture risk. Objective: This study [B-vitamins for the PRevention Of Osteoporotic Fractures (B-PROOF)] aimed to determine whether vitamin B-12 and folic acid supplementation reduces osteoporotic fracture incidence in hyperhomocysteinemic elderly individuals. Design: This was a double-blind, randomized, placebo-controlled trial in 2919 participants aged =65 y with elevated homocysteine concentrations (12–50 µmol/L). Participants were assigned to receive daily 500 µg vitamin B-12 plus 400 µg folic acid or placebo supplementation for 2 y. Both intervention and placebo tablets also contained 600 IU vitamin D3. The primary endpoint was time to first osteoporotic fracture. Exploratory prespecified subgroup analyses were performed in men and women and in individuals younger than and older than age 80 y. Data were analyzed according to intention-to-treat and per-protocol principles. Results: Osteoporotic fractures occurred in 61 persons (4.2%) in the intervention group and 75 persons (5.1%) in the placebo group. Osteoporotic fracture risk was not significantly different between groups in the intention-to-treat analyses (HR: 0.84; 95% CI: 0.58, 1.21) or per-protocol analyses (HR: 0.81; 95% CI: 0.54, 1.21). For persons >80 y, in per-protocol analyses, osteoporotic fracture risk was lower in the intervention group than in the placebo group (HR: 0.27; 95% CI: 0.10, 0.74). The total number of adverse events (including mortality) did not differ between groups. However, 63 and 42 participants in the intervention and placebo groups, respectively, reported incident cancer (HR: 1.56; 95% CI: 1.04, 2.31). Conclusions: These data show that combined vitamin B-12 and folic acid supplementation had no effect on osteoporotic fracture incidence in this elderly population. Exploratory subgroup analyses suggest a beneficial effect on osteoporotic fracture prevention in compliant persons aged >80 y. However, treatment was also associated with increased incidence of cancer, although the study was not designed for assessing cancer outcomes. Therefore, vitamin B-12 plus folic acid supplementation cannot be recommended at present for fracture prevention in elderly people. The B-PROOF study was registered with the Netherlands Trial Register (trialregister.nl) as NTR1333 and at clinicaltrials.gov as NCT00696414.
B-vitamin levels and genetics of hyperhomocysteinemia are not associated with arterial stiffness
Dijk, S.C. van; Enneman, A.W. ; Meurs, J. van; Swart, K.M.A. ; Ham, A.H. van; Wijngaarden, J.P. van; Brouwer, E.M. ; Zwaluw, N.L. van der; Schoor, M.M. ; Dhonukshe-Rutten, R.A.M. ; Groot, C.P.G.M. de; Lips, P. ; Geleijnse, J.M. ; Feskens, E.J.M. - \ 2014
Nutrition, Metabolism & Cardiovascular Diseases 24 (2014)7. - ISSN 0939-4753 - p. 760 - 766.
cardiovascular-disease - homocysteine levels - aortic stiffness - vascular-disease - risk - deficiency - mortality - folate - adults - cells
Background and aims - Hyperhomocysteinemia is associated with arterial stiffness, but underlying pathophysiological mechanisms explaining this association are to be revealed. This study was aimed to explore two potential pathways concerning the one-carbon metabolism. A potential causal effect of homocysteine was explored using a genetic risk score reflecting an individual's risk of having a long-term elevated plasma homocysteine level and also associations with B-vitamin levels were investigated. Methods and results - Baseline cross-sectional data of the B-PROOF study were used. In the cardiovascular subgroup (n = 567, 56% male, age 72.6 ± 5.6 yrs) pulse wave velocity (PWV) was determined using applanation tonometry. Plasma concentrations of vitamin B12, folate, methylmalonic acid (MMA) and holo transcobalamin (holoTC) were assessed and the genetic risk score was based on 13 SNPs being associated with elevated plasma homocysteine. Associations were examined using multivariable linear regression analysis. B-vitamin levels were not associated with PWV. The genetic risk score was also not associated with PWV. However, the homocysteine–gene interaction was significant (p <0.001) in the association of the genetic risk score and PWV. Participants with the lowest genetic risk of having long-term elevated homocysteine levels, but with higher measured homocysteine levels, had the highest PWV levels. Conclusion - Homocysteine is unlikely to be causally related to arterial stiffness, because there was no association with genetic variants causing hyperhomocysteinemia, whereas non-genetically determined hyperhomocysteinemia was associated with arterial stiffness. Moreover, the association between homocysteine and arterial stiffness was not mediated by B-vitamins. Possibly, high plasma homocysteine levels reflect an unidentified factor, that causes increased arterial stiffness.
A structural equation modelling approach to explore the role of B vitamins and immune markers in lung cancer risk
Baltar, V.T. ; Xun, W.W. ; Johansson, M. ; Bueno-de-Mesquita, B. ; Boshuizen, H.C. ; Gils, C.H. van; Onland-Moret, C.N. - \ 2013
European Journal of Epidemiology 28 (2013)8. - ISSN 0393-2990 - p. 677 - 688.
one-carbon metabolism - dna methylation - indoleamine 2,3-dioxygenase - colorectal-cancer - system activation - folate - infection - men - polymorphisms - neopterin
The one-carbon metabolism (OCM) is considered key in maintaining DNA integrity and regulating gene expression, and may be involved in the process of carcinogenesis. Several B-vitamins and amino acids have been implicated in lung cancer risk, via the OCM directly as well as immune system activation. However it is unclear whether these factors act independently or through complex mechanisms. The current study applies structural equations modelling (SEM) to further disentangle the mechanisms involved in lung carcinogenesis. SEM allows simultaneous estimation of linear relations where a variable can be the outcome in one equation and the predictor in another, as well as allowing estimation using latent variables (factors estimated by correlation matrix). A large number of biomarkers have been analysed from 891 lung cancer cases and 1,747 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Four putative mechanisms in the OCM and immunity were investigated in relation to lung cancer risk: methionine-homocysteine metabolism, folate cycle, transsulfuration, and mechanisms involved in inflammation and immune activation, all adjusted for tobacco exposure. The hypothesized SEM model confirmed a direct and protective effect for factors representing methionine-homocysteine metabolism (p = 0.020) and immune activation (p = 0.021), and an indirect protective effect of folate cycle (p = 0.019), after adjustment for tobacco smoking. In conclusion, our results show that in the investigation of the involvement of the OCM, the folate cycle and immune system in lung carcinogenesis, it is important to consider complex pathways (by applying SEM) rather than the effects of single vitamins or nutrients (e.g. using traditional multiple regression). In our study SEM were able to suggest a greater role of the methionine-homocysteine metabolism and immune activation over other potential mechanisms.
Genetic Variation in Vitamin B-12 Content of Bovine Milk and Its Association with SNP along the Bovine Genome
Rutten, M.J.M. ; Bouwman, A.C. ; Sprong, R.C. ; Arendonk, J.A.M. van; Visker, M.H.P.W. - \ 2013
PLoS One 8 (2013)4. - ISSN 1932-6203 - 6 p.
homocysteine - population - lactation - binding - cobalt - folate - cells - cows - fat
Vitamin B-12 (also called cobalamin) is essential for human health and current intake levels of vitamin B-12 are considered to be too low. Natural enrichment of the vitamin B-12 content in milk, an important dietary source of vitamin B-12, may help to increase vitamin B-12 intake. Natural enrichment of the milk vitamin B-12 content could be achieved through genetic selection, provided there is genetic variation between cows with respect to the vitamin B-12 content in their milk. A substantial amount of genetic variation in vitamin B-12 content was detected among raw milk samples of 544 first-lactation Dutch Holstein Friesian cows. The presence of genetic variation between animals in vitamin B-12 content in milk indicates that the genotype of the cow affects the amount of vitamin B-12 that ends up in her milk and, consequently, that the average milk vitamin B-12 content of the cow population can be increased by genetic selection. A genome-wide association study revealed significant association between 68 SNP and vitamin B-12 content in raw milk of 487 first-lactation Dutch Holstein Friesian cows. This knowledge facilitates genetic selection for milk vitamin B-12 content. It also contributes to the understanding of the biological mechanism responsible for the observed genetic variation in vitamin B-12 content in milk. None of the 68 significantly associated SNP were in or near known candidate genes involved in transport of vitamin B-12 through the gastrointestinal tract, uptake by ileum epithelial cells, export from ileal cells, transport through the blood, uptake from the blood, intracellular processing, or reabsorption by the kidneys. Probably, associations relate to genes involved in alternative pathways of well-studied processes or to genes involved in less well-studied processes such as ruminal production of vitamin B-12 or secretion of vitamin B-12 by the mammary gland
Nutritional Genetics: The Case of Alcohol and the MTHFR C677T Polymorphism in relation to homocysteine in a Black South African Population
Nienaber-Rousseau, C. ; Pisa, P.T. ; Venster, C.S. ; Ellis, S.M. ; Kruger, A. ; Moss, S. ; Boonstra, A. ; Towers, G.W. - \ 2013
Journal of Nutrigenetics and Nutrigenomics 6 (2013)2. - ISSN 1661-6499 - p. 61 - 72.
coronary-heart-disease - cardiovascular risk-factors - plasma total homocysteine - methylenetetrahydrofolate reductase - consumption - hyperhomocysteinemia - folate - determinants - metaanalysis - frequency
Background/Aims: It is unknown whether the effect of alcohol consumption on homocysteine (Hcy) is modulated by the methylenetetrahydrofolate reductase (MTHFR) C677T. We explored this hypothesized effect by analyzing cross-sectional data of 1,827 black South Africans. Methods: Total Hcy concentrations were determined by fluorescence polarization immunoassay and the genotype through polymerase chain reaction-based RFLP analysis. Results: Subjects harboring the 677 TT genotype had the highest Hcy. Among subjects harboring the 677 CC genotype, men had higher Hcy (p = 0.04). Age and gamma-glutamyltransferase (GGT) correlated best (r = 0.26 and r = 0.27; p <0.05), while the percentage carbohydrate-deficient transferrin and the B vitamins correlated weakly (r <0.1; p <0.05) with Hcy. Hcy was positively associated with the reported alcohol intake (p = 0.01). There was no interaction between alcohol consumption and the MTHFR 677 CC or CT genotypes (p > 0.05) for Hcy concentrations; however, an interaction was determined for GGT and the MTHFR genotype (p = 0.02). Age, GGT, gender, MTHFR and vitamin B6 explained 16.8% of the variation in Hcy (p <0.01). Conclusion: The determined interactions might result in differences in the risk conveyed through Hcy with regard to disease development in those with unfavorable GGT concentrations.
DNA methylation and cognitive functioning in healthy older adults
Schiepers, O.J.G. ; Boxtel, M.P.J. van; Groot, R.H.M. ; Jolles, J. ; Kok, F.J. ; Verhoef, P. ; Durga, J. - \ 2012
British Journal of Nutrition 107 (2012)5. - ISSN 0007-1145 - p. 744 - 748.
physical-activity - common mutation - homocysteine - folate - disorders - reductase - disease
Long-term supplementation with folic acid may improve cognitive performance in older individuals. The relationship between folate status and cognitive performance might be mediated by changes in methylation capacity, as methylation reactions are important for normal functioning of the brain. Although aberrant DNA methylation has been implicated in neurodevelopmental disorders, the relationship between DNA methylation status and non-pathological cognitive functioning in human subjects has not yet been investigated. The present study investigated the associations between global DNA methylation and key domains of cognitive functioning in healthy older adults. Global DNA methylation, defined as the percentage of methylated cytosine to total cytosine, was measured in leucocytes by liquid chromatography-MS/MS, in 215 men and women, aged 50-70 years, who participated in the Folic Acid and Carotid Intima-Media Thickness (FACIT) study (clinical trial registration number NCT00110604). Cognitive performance was assessed by means of the Visual Verbal Word Learning Task, the Stroop Colour-Word Interference Test, the Concept Shifting Test, the Letter-Digit Substitution Test and the Verbal Fluency Test. Using hierarchical linear regression analyses adjusted for age, sex, level of education, alcohol consumption, smoking status, physical activity, erythrocyte folate concentration and 5,10-methylenetetrahydrofolate reductase 677 C ! T genotype, we found that global DNA methylation was not related to cognitive performance on any of the domains measured. The present study results do not support the hypothesis that global DNA methylation, as measured in leucocytes, might be associated with cognitive functioning in healthy older individuals.
Fruit and vegetable consumption and risk of aggressive and non-aggressive urothelial cell carcinomas in the European prospective investigation into cancer and nutrition
Ros, M. ; Bueno-de-Mesquita, H.B. ; Kampman, E. ; Büchner, F.L. ; Aben, K.K. ; Egevad, L. ; Overvad, K. ; Tjonneland, A. ; Roswall, N. ; Clavel-Chapelon, F. ; Boutron-Ruault, M.C. ; Moiros, S. ; Kaaks, R. ; Teucher, B. ; Weikert, S. ; Ruesten, A.V. ; Trichopoulou, A. ; Naska, A. ; Benetou, V. ; Saieva, C. ; Pala, V. ; Ricceri, F. ; Tumino, R. ; Mattiello, A. ; Peeters, P.H.M. ; Gils, C.H. van; Gram, I.T. ; Engeset, D. ; Chirlaque, M.D. ; Ardanazx, E. ; Rodriguez, L. - \ 2012
European Journal of Cancer 48 (2012)17. - ISSN 0959-8049 - p. 3267 - 3277.
bladder-cancer - vitamin-c - prospective cohort - carotenoids - smoking - diet - carcinogenesis - prevention - nutrient - folate
Background - Many epidemiological studies have examined fruit and vegetable consumption in relation to the risk of urothelial cell carcinoma (UCC) of the bladder, but results are inconsistent. The association between fruit and vegetable consumption and UCC risk may vary by bladder tumour aggressiveness. Therefore, we examined the relation between fruit and vegetable consumption and the risk of aggressive and non-aggressive UCC in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods - After 8.9 years of follow-up, 947 UCC were diagnosed among 468,656 EPIC participants. Of these, 421 could be classified as aggressive UCC and 433 as non-aggressive UCC cases. At recruitment, fruit and vegetable consumption was assessed by validated dietary questionnaires. Multivariable hazard ratios were estimated using Cox regression stratified by age, sex and center and adjusted for smoking status, duration and intensity of smoking, and energy intake. Results - Total consumption of fruits and vegetables was not associated with aggressive UCC nor with non-aggressive UCC. A 25 g/day increase in leafy vegetables and grapes consumption was associated with a reduced risk of non-aggressive UCC (hazard ratio (HR) 0.88; 95% confidence interval (CI) 0.78–1.00 and HR 0.87; 95% CI 0.77–0.98, respectively), while the intake of root vegetables was inversely associated with risk of aggressive UCC (HR 0.87; 95% CI 0.77–0.98). Conclusion - Our study did not confirm a protective effect of total fruit and/or vegetable consumption on aggressive or non-aggressive UCC. High consumption of certain types of vegetables and of fruits may reduce the risk of aggressive or non-aggressive UCC; however chance findings cannot be excluded.
Transformations of summary statistics as input in meta-analysis for linear dose-response models on a logarithmic scale: a methodology developed within EURRECA
Souverein, O.W. ; Dullemeijer, C. ; Veer, P. van 't; Voet, Hilko van der - \ 2012
BMC Medical Research Methodology 12 (2012). - ISSN 1471-2288
nutritional epidemiology - vitamin-b-12 intake - homocysteine - folate - humans - women - population - error
Background: To derive micronutrient recommendations in a scientifically sound way, it is important to obtain and analyse all published information on the association between micronutrient intake and biochemical proxies for micronutrient status using a systematic approach. Therefore, it is important to incorporate information from randomized controlled trials as well as observational studies as both of these provide information on the association. However, original research papers present their data in various ways. Methods: This paper presents a methodology to obtain an estimate of the dose-response curve, assuming a bivariate normal linear model on the logarithmic scale, incorporating a range of transformations of the original reported data. Results: The simulation study, conducted to validate the methodology, shows that there is no bias in the transformations. Furthermore, it is shown that when the original studies report the mean and standard deviation or the geometric mean and confidence interval the results are less variable compared to when the median with IQR or range is reported in the original study. Conclusions: The presented methodology with transformations for various reported data provides a valid way to estimate the dose-response curve for micronutrient intake and status using both randomized controlled trials and observational studies.
The preconception Mediterranean dietary pattern in couples undergoing in vitro fertilization/intracytoplasmic sperm injection treatment increases the chance of pregnancy
Vujkovic, M. ; Vries, J.H.M. de; Lindemans, J. ; Macklon, N.S. ; Spek, P.J. van der; Steegers, E.A.P. ; Steegers-Theunissen, R.P.M. - \ 2010
Fertility and Sterility 94 (2010)6. - ISSN 0015-0282 - p. 2096 - 2101.
life-style factors - folic-acid - energy-intake - homocysteine - fertility - folate - implantation - performance - population - impact
Objective: To investigate associations between preconception dietary patterns and IVF/intracytoplasmic sperm injection (ICSI) outcomes validated by biomarkers of the homocysteine pathway. Design: Observational prospective study. Setting: A tertiary referral fertility clinic at the Erasmus University Medical Centre, Rotterdam, The Netherlands. Patient(s): One hundred sixty-one couples undergoing IVF/ICSI treatment. Intervention(s): No interventions other than the Dutch governmental recommendation of folic acid. Main Outcome Measure(s): Dietary patterns, blood and follicular fluid concentrations of folate, vitamin B12, vitamin B6, homocysteine, and fertilization rate, embryo quality, and pregnancy. Result(s): In women, two dietary patterns were identified. The "health conscious-low processed" dietary pattern (variation explained 12.1%) was characterized by high intakes of fruits, vegetables, fish, and whole grains and low intakes of snacks, meats, and mayonnaise, and positively correlated with red blood cell folate (beta=0.07). The "Mediterranean" dietary pattern (variation explained 9.1%), that is, high intakes of vegetable oils, vegetables, fish, and legumes and low intakes of snacks, was positively correlated with red blood cell folate (beta=0.13), and vitamin B6 in blood (beta=0.09) and follicular fluid (beta=0.18). High adherence by the couple to the "Mediterranean" diet increased the probability of pregnancy, odds ratio 1.4 (95% confidence interval 1.0-1.9). Conclusion(s): A preconception "Mediterranean" diet by couples undergoing IVF/ICSI treatment contributes to the success of achieving pregnancy. (Fertil Steril (R) 2010; 94: 2096-101. (C) 2010 by American Society for Reproductive Medicine.)
Nutritional concerns, health and survival in old age
Groot, C.P.G.M. de; Staveren, W.A. van - \ 2010
Biogerontology 11 (2010)5. - ISSN 1389-5729 - p. 597 - 602.
vitamin-d - mediterranean diet - fractures - deficiency - disease - people - folate
The ageing process is-apart from chance or good luck-not only influenced by factors intrinsic to the individual, but also by extrinsic factors that include environmental and lifestyle variables. This paper deals with the epidemiological evidence for the role of dietary patterns and key nutritional concerns in relation to survival and ageing related disorders that present themselves in later life. Dietary patterns, such as the Mediterranean diet, characterized by mainly plant foods including protective factors e.g. vegetables, nuts and monounsaturated fatty acids and excluding harmful factors e.g. trans-fatty acids and foods with a high glycemic factor, appear to be relevant even in old age. Specific nutritional concerns focus on general undernutrition, vitamin D and vitamin B(12). Prevalence of nutritional inadequacies, diagnostic criteria, causes and health consequences are described. The paper ends with recommendations for guidance on healthy diets for elderly people. An important challenge should be research to further expand the knowledge base, acknowledging the complexity of the ageing process and integrating different dimensions of research into human healthy ageing in properly designed studies. In the mean time reversing poor adherence to existing guidelines for a healthy diet remains a first challenge in public health nutritional practices
Consumption of vegetables and fruit and the risk of bladder cancer in the European Prospective Investigation into Cancer and Nutrition
Büchner, F.L. ; Bueno de Mesquita, H.B. ; Ros, M.M. ; Kampman, E. - \ 2009
International Journal of Cancer 125 (2009)11. - ISSN 0020-7136 - p. 2643 - 2651.
vitamin-c - cigarette-smoking - prospective cohort - carotenoids - epidemiology - folate - diet - food
Previous epidemiologic studies found inconsistent associations between vegetables and fruit consumption and the risk of bladder cancer. We therefore investigated the association between vegetable and fruit consumption and the risk of bladder cancer among participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Data on food consumption and complete follow-up for cancer occurrence was available for a total of 478,533 participants, who were recruited in 10 European countries. Estimates of rate ratios were obtained by Cox proportional hazard models, stratified by age at recruitment, gender and study centre, and adjusted for total energy intake, smoking status, duration of smoking and lifetime intensity of smoking. A calibration study in a subsample was used to control for dietary measurement errors. After a mean follow-up of 8.7 years, 1015 participants were newly diagnosed with bladder cancer. Increments of 100 g/day in fruit and vegetable consumption combined did not affect bladder cancer risk (i.e., calibrated HR = 0.98; 95%CI: 0.95–1.01). Borderline statistically significant lower bladder cancer risks were found among never smokers with increased consumption of fruit and vegetables combined (HR = 0.94 95%CI: 0.87–1.00 with increments of 100 g/day; calibrated HR = 0.92 95%CI 0.79–1.06) and increased consumption of apples and pears (hard fruit; calibrated HR = 0.90 95%CI: 0.82–0.98 with increments of 25 g/day). For none of the associations a statistically significant interaction with smoking status was found. Our findings do not support an effect of fruit and vegetable consumption, combined or separately, on bladder cancer risk.
Inhibition of methylation and changes in gene expression in relation to neural tube defects
Linden, I.J. van der; Heil, S.G. ; Egmont-Petersen, M. van; Straaten, H.W. ; Heijer, M. den - \ 2008
Birth defects research. Part A, Clinical and molecular teratology 82 (2008)10. - ISSN 1542-0752 - p. 676 - 683.
factor-i - methylenetetrahydrofolate reductase - serine/threonine kinase - caenorhabditis-elegans - mammalian development - common mutation - risk-factor - dna - serine - folate
BACKGROUND: An impaired DNA methylation has been suggested to underlie the complex etiology of neural tube defects (NTDs). Previously, we have demonstrated that inhibition of methylation by periodate oxidized adenosine (Adox) results in a widening of the anterior neuropore (ANP) in our in vitro chick embryo model. Since DNA methylation is the chief regulator of gene expression, we hypothesize that inhibition of methylation by Adox in our in vitro chick embryo model will affect the expression of genes that may be involved in neurulation. In the present study, we therefore examined differential gene expression between Adox-treated and control chick embryos, using the Affymetrix Genechip Chicken Genome Array. METHODS: Chick embryos of 4/5 somites were cultured in vitro with saline (control) or Adox and cranial parts were excised. Gene expression profiling was determined using the Affymetrix Genechip Chicken Genome Array on RNA isolated from two pools of Adox-treated cranial parts (n = 12) and two pools of saline-treated cranial parts (n = 12). Microarray data were validated by QPCR analysis. RESULTS: In the Adox-treated chick embryos, 45 probesets were up-regulated (fold 2.0, p <0.05) and 32 probesets were down-regulated (fold 0.5, p <0.05). Of the 15 genes selected for QPCR analysis, the up-regulation of phosphoserine phosphatase (PSPH), unc-51-like kinase 1 (ULK1), and chemokine (C-X-C motif) ligand 12/stromal cell-derived factor 1 (CXCL12/SDF-1) was confirmed. CONCLUSIONS: Inhibition of methylation by Adox affects gene expression in our in vitro chick embryo model. Further research will focus on the gene-specific methylation patterns of PSPH, ULK1, and CXCL12/SDF-1 and the role of the products of these genes in neurulation.
Retinol and Riboflavin Supplementation Decreases the Prevalence of Anemia in Chinese Pregnant Women Taking Iron and Folic Acid Supplements 1-3
Aiguo, M. ; Schouten, E.G. ; Zhang, F.Z. ; Kok, F.J. ; Yang, F. ; Jiang, D.C. ; Sun, Y.Y. ; Han, X.X. - \ 2008
The Journal of Nutrition 138 (2008)10. - ISSN 0022-3166 - p. 1946 - 1950.
vitamin-a-deficiency - clinical-trial - folate - adaptation - health
In rural China, many pregnant women in their third trimester suffer from anemia (48%) and iron deficiency (ID; 42%), often with coexisting deficiencies of retinol and riboflavin. We investigated the effect of retinol and riboflavin supplementation in addition to iron plus folic acid on anemia and subjective well-being in pregnant women. The study was a 2-mo, double-blind, randomized trial. Subjects (n = 366) with anemia [hemoglobin (Hb) 105 g/L] were randomly assigned to 4 groups, all receiving 60 mg/d iron and 400 µg/d folic acid. The iron+folic acid (IF) group (n = 93) served as reference, the iron+folic acid+retinol group (IFA) (n = 91) was treated with 2000 µg retinol, the iron+folic acid+riboflavin group (IFB) (n = 91) with 1.0 mg riboflavin, and the iron+folic acid+retinol+riboflavin group (IFAB) (n = 91) with retinol and riboflavin. After the 2-mo intervention, the Hb concentration increased in all 4 groups (P <0.001). The increase in the IFAB group was 5.4 ± 1.1 g/L greater than in the IF group (P <0.001). The reduced prevalence of anemia (Hb <110g/L) and ID anemia were significantly greater in the groups supplemented with retinol and /or riboflavin than in the IF group. Moreover, gastrointestinal symptoms were less prevalent in the IFA group than in the IF group (P <0.05) and improved well-being was more prevalent in the groups receiving additional retinol and/or riboflavin than in the IF group (P <0.05). Thus, a combination of iron, folic acid, retinol, and riboflavin was more effective than iron plus folic acid alone. Multimicronutrient supplementation may be worthwhile for pregnant women in rural China.
Eight-fold increased risk for congenital heart defects in children carrying the nicotinamide N-methyltransferase polymorphism and exposed to medicines and low nicotinamide
Driel, L.M.J.W. van; Smedts, H.P.M. ; Helbing, W.A. ; Isaacs, A. ; Lindemans, J. ; Uitterlinden, A.G. ; Duijn, C.M. van; Vries, J.H.M. de; Steegers, E.A.P. ; Steegers-Theunissen, R.P.M. - \ 2008
European Heart Journal 29 (2008)11. - ISSN 0195-668X - p. 1424 - 1431.
plasma homocysteine - gene - pregnancy - malformations - multivitamin - association - methylation - supplements - folate - bias
Aims: Congenital heart defects (CHDs) have a multifactorial origin, in which subtle genetic factors and peri-conception exposures interact. We hypothesize that derangements in the homocysteine and detoxification pathways, due to a polymorphism in the nicotinamide N-methyltransferase (NNMT) gene, low maternal dietary nicotinamide intake, and medicine use in the peri-conception period, affect CHD risk. Methods and results: In 292 case and 316 control families, maternal peri-conception medicine use and low dietary intake of nicotinamide (13.8 mg/day) were independently associated with CHD risk [odds ratio (95% confidence interval) 1.6 (1.1¿2.3) and 1.5 (1.03¿2.3), respectively]. No significant association was found for the NNMT AG/AA genotype in mothers [0.9 (0.7¿1.3)], fathers [1.1 (0.8¿1.6)], or children [1.1 (0.8¿1.6)]. However, the combination of peri-conception medicine use, low dietary nicotinamide intake, and the NNMT AG/AA genotype in mothers or children showed risk of 2.7 (1.02¿8.1) and 8.8 (2.4¿32.5), respectively. Conclusion: Children carrying the NNMT A allele face additional CHD risk in combination with peri-conception exposure to medicines and/or a low dietary nicotinamide intake. These findings provide a first set of data against which future studies with larger sample sizes can be compared with.
Dietary intake of B6-9-12 vitamins, serum homocysteine levels and their association with depressive symptoms: the Zutphen Elderly Study
Kamphuis, M.H. ; Geerlings, M.I. ; Grobbee, D.E. ; Kromhout, D. - \ 2008
European Journal of Clinical Nutrition 62 (2008). - ISSN 0954-3007 - p. 939 - 945.
cognitive function - myocardial-infarction - community sample - dutch population - older women - folic-acid - follow-up - folate - men - scale
Objective: Low B-vitamin status and high levels of serum homocysteine are found in depressed inpatients, but results of population-based studies of this association are inconclusive. We investigated whether a low dietary intake of B6-9-12 vitamins and high levels of serum homocysteine are associated with depressive symptoms in elderly men. Methods: The study sample included a total of 332 men aged 70¿90 years who were free from cardiovascular diseases and diabetes at baseline in 1990. Depressive symptoms were measured with the Zung Self-rating Depression Scale at baseline in 1990 and dietary factors with the crosscheck dietary history method in 1985 and 1990. Serum levels of homocysteine were obtained in 1985. Multiple linear and logistic regression analyses were performed. Results: Dietary intake of folate (-1.19, 95% CI -2.03; -0.36) and vitamin B6 (-2.09, 95% CI -2.92; -1.26) per standard deviation increase was associated with lower levels of serum homocysteine, while vitamin B12 was not associated with serum homocysteine. Intake of folate, vitamin B6, vitamin B12 and levels of serum homocysteine were not related to depressive symptoms. Conclusions: Our results do not support the hypothesis that a low dietary intake of B6-9-12 vitamins and high levels of serum homocysteine are related to depression in healthy elderly men.
|What can we learn from the FACIT trial: A randomized, double blind, controlled trial
Durga, J. ; Boxtel, M.P.J. van; Schouten, E.G. ; Kok, F.J. ; Jolles, J. ; Katan, M.B. ; Verhoef, P. - \ 2007
Journal of Nutrition, Health and Aging 11 (2007)4. - ISSN 1279-7707 - p. 320 - 324.
folic-acid supplementation - cognitive function - memory performance - elderly-patients - homocysteine - dementia - vitamin-b-12 - disease - people - folate
Effects of Folic Acid Supplementation on Hearing in Older Adults: a Randomized, Controlled Trial
Durga, J. ; Verhoef, P. ; Anteunis, L.J.C. ; Schouten, E.G. ; Kok, F.J. - \ 2007
Annals of Internal Medicine 146 (2007)1. - ISSN 0003-4819 - p. 1 - 9.
cardiovascular risk - vitamin status - rat-brain - homocysteine - folate - population - disease - plasma - serum - hyperhomocysteinemia
Background: Age-related hearing loss is a common chronic condition of elderly persons. Low folate status has been associated with poor hearing. Objective: To determine whether folic acid supplementation slows age-related hearing loss. Design: Double-blind, randomized, placebo-controlled trial conducted from September 2000 to December 2004. Setting: The Netherlands. Participants: 728 older men and women recruited from municipal and blood bank registries with plasma total homocysteine concentrations 13 mu mol/L or greater serum and vitamin B-12 concentrations 200 pmol/L or greater at screening, and no middle ear dysfunction, unilateral hearing loss, or pathologic ear conditions unrelated to aging. Intervention: Daily oral folic acid (800 mu g) or placebo supplementation for 3 years. Measurements: 3-year change in hearing thresholds, assessed as the average of the pure-tone air conduction thresholds of both ears of the low (0.5-kHz, 1-kHz, and 2-kHz) and high (4-kHz, 6-kHz, and 8-kHz) frequencies. Results: Initial median hearing thresholds were 11.7 dB (interquartile range, 7.5 to 17.5 dB) for low frequencies and 34.2 dB (interquartile range, 22.5 to 50.0 dB) for high frequencies. Sixteen participants (2%) were lost to follow-up. After 3 years, thresholds of the low frequencies increased by 1.0 dB (95% CI, 0.6 to 1.4 dB) in the folic acid group and by 1.7 dB (CI, 1.3 to 2.1 dB) in the placebo group (difference, -0.7 dB [CI, -1.2 to -0.1 dB]; P = 0.020). Folic acid supplementation did not affect the decline in hearing high frequencies. Limitations: The strict criterion for participation on the basis of serum homocysteine concentrations limits extrapolation to the general population. Folic acid fortification of food was prohibited in the Netherlands during the study, so baseline folate levels in participants were about half of those found in the U. S. population. Conclusions: Folic acid supplementation slowed the decline in hearing of the speech frequencies associated with aging in a population from a country without folic acid fortification of food. The effect requires confirmation, especially in populations from countries with folic acid fortification programs.