- A. Botma (1)
- M.L. Bots (2)
- M.P.J. Boxtel van (1)
- J.J.M. Castenmiller (1)
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- J. Durga (4)
- J. Durga (1)
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- S.M. Ellis (2)
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- M.W. Fraaije (1)
- J.F. Gregory III (1)
- J.L. Harryvan (1)
- A. Heck (1)
- M. Heijer den (1)
- S.G. Heil (1)
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- D.B. Janssen (1)
- J. Jolles (1)
- R.J. Jong (1)
- A.Y. Jung (2)
- N.M. Kamerbeek (1)
- E. Kampman (2)
- M.B. Katan (2)
- J.H. Kleibeuker (1)
- A. Klein (1)
- M. Klerk (1)
- C. Kluft (1)
- F.J. Kok (5)
- R.M. Kok (1)
- I.P.C. Krapels (1)
- A. Kruger (1)
- I.J. Linden van der (1)
- P. Mastroiacovo (1)
- I.F.W. McDowell (1)
- H.M. McNulty (1)
- A. Melse (1)
- S. Moss (2)
- M.R. Müller (1)
- F.M. Nagengast (1)
- C. Nienaber-Rousseau (2)
- P.T. Pisa (1)
- P. Sanderson (1)
- E.G. Schouten (4)
- E. Siebelink (1)
- Y. Smulders (1)
- R.P.M. Steegers-Theunissen (1)
- G.R.S. Steenge (1)
- H.W. Straaten (1)
- N. Tahallah (1)
- G.W. Towers (2)
- H.F.A. Vasen (1)
- C.S. Venster (1)
- P. Verhoef (6)
- C. Vermeij-Keers (1)
- M. Verwei (1)
- T. Vliet van (1)
- C.E. West (1)
- R.M. Winkels (1)
Dietary B vitamin and methionine intake and MTHFR C677T genotype on risk of colorectal tumors in Lynch syndrome: the GEOLynch cohort study
Jung, A.Y. ; Duijnhoven, F.J.B. van; Nagengast, F.M. ; Botma, A. ; Heine-Bröring, R.C. ; Kleibeuker, J.H. ; Vasen, H.F.A. ; Harryvan, J.L. ; Winkels, R.M. ; Kampman, E. - \ 2014
Cancer Causes and Control 25 (2014)9. - ISSN 0957-5243 - p. 1119 - 1129.
food-frequency questionnaire - nonpolyposis colon-cancer - folic-acid supplementation - biomarker-based validity - mismatch-repair genes - body-mass index - methylenetetrahydrofolate reductase - folate intake - plasma folate - cigarette-smoking
Purpose Dietary intake of B vitamins and methionine, essential components of DNA synthesis and methylation pathways, may influence colorectal tumor (CRT) development. The impact of B vitamins on colorectal carcinogenesis in individuals with Lynch syndrome (LS) is unknown but is important given their high lifetime risk of developing neoplasms. The role of MTHFR C677T genotype in modifying these relationships in LS individuals is also unclear. We investigated associations between dietary intakes of folate, vitamins B2, B6, B12, and methionine and CRT development in a prospective cohort study of 470 mismatch repair gene mutation carriers. Methods Dietary intakes were assessed by food frequency questionnaire. Cox regression models with robust sandwich covariance estimation, adjusted for age, sex, physical activity, number of colonoscopies during person-time, NSAID use, and mutual vitamins were used to calculate hazard ratios (HRs) and 95 % confidence intervals (95 % CIs). Analyses were also stratified by MTHFR C677T genotype. Results During a median person-time of 28.0 months, 131 persons developed a CRT. Fifty-one of these persons developed an incident colorectal adenoma, while there were four persons who developed an incident colorectal carcinoma. Compared to the lowest tertile of intake, adjusted HRs (95 % CIs) for CRT development in the highest tertile were 1.06 (0.59–1.91) for folate, 0.77 (0.39–1.51) for vitamin B2, 0.98 (0.59–1.62) for vitamin B6, 1.24 (0.77–2.00) for vitamin B12, and 1.36 (0.83–2.20) for methionine. Low vitamin B2 and low methionine intake were statistically significantly associated with an increased risk of CRT in MTHFR 677TT individuals compared to a combined reference of persons with low intake and CC genotype. Conclusions There was no suggestion that intake of any dietary B vitamin or methionine was associated with CRT development among those with LS.
Gene–environment and gene–gene interactions of specific MTHFR, MTR and CBS gene variants in relation to homocysteine in black South Africans
Nienaber-Rousseau, C. ; Ellis, S.M. ; Moss, S. ; Boonstra, A. ; Towers, G.W. - \ 2013
Gene 530 (2013)1. - ISSN 0378-1119 - p. 113 - 118.
beta-synthase gene - coronary-artery-disease - plasma homocysteine - methylenetetrahydrofolate reductase - methionine synthase - risk-factors - cardiovascular-disease - heart-disease - vascular-disease - high prevalence
The methylenetetrahydrofolate reductase (MTHFR), cystathione-beta-synthase (CBS) and methionine synthase (MTR) genes interact with each other and the environment. These interactions could influence homocysteine (Hcy) and diseases contingent thereon. We determined single nucleotide polymorphisms (SNPs) within these genes, their relationships and interactions with total Hcy concentrations within black South Africans to address the increased prevalence of diseases associated with Hcy. The MTHFR 677 TT and MTR 2756 AA genotypes were associated with higher Hcy concentrations (16.6 and 10.1 mu mol/L; p <0.05) compared to subjects harboring the MTHFR 677 CT/CC and the MTR 2756 AG genotypes (10.5, 9.7 and 9.5 mu mol/L, respectively). The investigated CBS genotypes did not influence Hcy. We demonstrated interactions between the area of residence and the CBS T833C/844ins68 genotypes (p = 0.005) so that when harboring the wildtype allele, rural subjects had significantly higher Hcy than their urban counterparts, but when hosting the variant allele the environment made no difference to Hcy. Between the CBS T833C/844ins68 or G9276A and MTHFR C677T genotypes, there were two-way interactions (p = 0.003 and = 0.004, respectively), with regard to Hcy. Subjects harboring the MTHFR 677 TT genotype in combination with the CBS 833 TT/homozygous 844 non-insert or the MTHFR 677 IF genotype in combination with the CBS 9276 GA/GG displayed higher Hcy concentrations. Therefore, some of the investigated genotypes affected Hcy; residential area changed the way in which the CBS T833C/844ins68 SNPs influenced Hcy concentrations highlighting the importance of environmental factors; and gene-gene interactions allude to epistalic effects. (C) 2013 Elsevier B.V. All rights reserved.
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.
No Effect of Folic Acid Supplementation on Global DNA Methylation in Men and Women with Moderately Elevated Homocysteine
Jung, A.Y. ; Smulders, Y. ; Verhoef, P. ; Kok, F.J. ; Blom, H. ; Kok, R.M. ; Kampman, E. ; Durga, J. - \ 2011
PLoS ONE 6 (2011)9. - ISSN 1932-6203
methylenetetrahydrofolate reductase - folate supplementation - plasma homocysteine - colorectal-cancer - controlled-trial - common mutation - older-adults - human-colon - hypomethylation - gene
A global loss of cytosine methylation in DNA has been implicated in a wide range of diseases. There is growing evidence that modifications in DNA methylation can be brought about by altering the intake of methyl donors such as folate. We examined whether long-term daily supplementation with 0.8 mg of folic acid would increase global DNA methylation compared with placebo in individuals with elevated plasma homocysteine. We also investigated if these effects were modified by MTHFR C677T genotype. Two hundred sixteen participants out of 818 subjects who had participated in a randomized double-blind placebo-controlled trial were selected, pre-stratified on MTHFR C677T genotype and matched on age and smoking status. They were allocated to receive either folic acid (0.8 mg/d; n = 105) or placebo treatment (n = 111) for three years. Peripheral blood leukocyte DNA methylation and serum and erythrocyte folate were assessed. Global DNA methylation was measured using liquid chromatography-tandem mass spectrometry and expressed as a percentage of 5-methylcytosines versus the total number of cytosine. There was no difference in global DNA methylation between those randomized to folic acid and those in the placebo group (difference = 0.008, 95%CI = -20.05,0.07, P = 0.79). There was also no difference between treatment groups when we stratified for MTHFR C677T genotype (CC, n = 76; CT, n = 70; TT, n = 70), baseline erythrocyte folate status or baseline DNA methylation levels. In moderately hyperhomocysteinemic men and women, long-term folic acid supplementation does not increase global DNA methylation in peripheral blood leukocytes.
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.
Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, 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
The Lancet 369 (2007)9557. - ISSN 0140-6736 - p. 208 - 216.
participants aged 24-81 - normative data - methylenetetrahydrofolate reductase - memory performance - alzheimers-disease - vascular-disease - elderly-patients - homocysteine - education - folate
Background Low folate and raised homocysteine concentrations in blood are associated with poor cognitive performance in the general population. As part of the FACIT trial to assess the effect of folic acid on markers of atherosclerosis in men and women aged 50-70 years with raised plasma total homocysteine and normal serum vitamin B-12 at screening, we report here the findings for the secondary endpoint: the effect of folic acid supplementation on cognitive performance. Methods Our randomised, double blind, placebo controlled study took place between November, 1999, and December, 2004, in the Netherlands. We randomly assigned 818 participants 800 mu g daily oral folic acid or placebo for 3 years. The effect on cognitive performance was measured as the difference between the two groups in the 3-year change in performance for memory, sensorimotor speed, complex speed, information processing speed, and word fluency. Analysis was by intention-to-treat. This trial is registered with clinicaltrials.gov with trial number NCT00110604. Findings Serum folate concentrations increased by 576% (95% CI 539 to 614) and plasma total homocysteine concentrations decreased by 26% (24 to 28) in participants taking folic acid compared with those taking placebo. The 3-year change in memory (difference in Z scores 0.132, 95% CI 0.032 to 0.233), information processing speed (0.087, 0.016 to 0.158) and sensorimotor speed (0.064, -0.001 to 0.129) were significantly better in the folic acid group than in the placebo group. Interpretation Folic acid supplementation for 3 years significantly improved domains of cognitive function that tend to decline with age.
Association of folate with hearing is dependent on the 5, 10-methylenetetrahydrofolate reductase 677C-->T mutation
Durga, J. ; Anteunis, L.J.C. ; Schouten, E.G. ; Bots, M.L. ; Kok, F.J. ; Verhoef, P. - \ 2006
Neurobiology of aging 27 (2006)3. - ISSN 0197-4580 - p. 482 - 489.
cardiovascular risk-factors - methylenetetrahydrofolate reductase - homocysteine concentrations - common mutation - disease - plasma - epidemiology - atherosclerosis - vitamin-b-12 - impairment
Vascular disease and its risk factors have been associated with the age-related hearing loss. We examined the association of elevated plasma homocysteine and its determinants with hearing levels. Pure-tone air conduction thresholds in 728 individuals with sensorineural hearing loss were not associated with homocysteine, erythrocyte folate and Vitamin B6. Low concentrations of serum folate and Vitamin B12 were associated with better hearing. When folate status was below the median, 5,10-methylenetetrahydrofolate reductase (MTHFR) 677TT homozygotes had similar hearing levels to subjects with a C allele. However, when folate status was above the median, MTHFR 677TT homozygotes had on an average 5 dB (p = 0.037) and 2.6 dB (p = 0.021) lower PTA-high and PTA-low hearing thresholds, respectively, than the subjects with a 677C allele. The relationship between serum folate and hearing thresholds appeared to be dependent on MTHFR 677 genotype (CC, r = 0.13, p = 0.034; TT, r = -0.10, p = 0.291). This supports the hypothesis that a greater one-carbon moiety commitment to de novo synthesis of nucleotides and an increase in formyl-folate derivatives relative to methyl-folate derivatives is protective for hearing.
Nutrition and Genes in the Development of Orofacial Clefting
Krapels, I.P.C. ; Vermeij-Keers, C. ; Müller, M.R. ; Klein, A. ; Steegers-Theunissen, R.P.M. - \ 2006
Nutrition Reviews 64 (2006)6. - ISSN 0029-6643 - p. 280 - 288.
growth-factor-alpha - embryonic palatal tissue - retinoid-x-receptor - tgf-beta isoforms - sonic-hedgehog - oral clefts - folic-acid - methylenetetrahydrofolate reductase - craniofacial morphogenesis - differential expression
Clefts of the lip, alveolus, and/or palate, which are called orofacial clefts (OFC), occur in 0.5 to 3 per 1000 live and stillbirths. The pathogenesis of these congenital malformations remains largely unknown, but evidence is increasing that both nutritional and genetic factors are involved. Unlike genetic factors, nutritional causes can be corrected and may therefore contribute to the prevention of OFC. The goal of this review is to summarize the embryogenesis and genes involved in OFC, and to give an overview of the nutrients and related genes in humans. Improving our knowledge of the role of nutrition, genes, and their interactions in the pathogenesis of OFC may stimulate the development of nutritional interventions for OFC prevention in the future.
Bioavailability of folic acid from fortified pasteurised and UHT-treated milk in humans
Jong, R.J. ; Verwei, M. ; West, C.E. ; Vliet, T. van; Siebelink, E. ; Berg, H. van den; Castenmiller, J.J.M. - \ 2005
European Journal of Clinical Nutrition 59 (2005)8. - ISSN 0954-3007 - p. 906 - 913.
folate-binding-protein - plasma homocysteine concentrations - neural-tube defects - methylenetetrahydrofolate reductase - food fortification - vascular-disease - common mutation - dietary-folate - risk factor - cows milk
Objective The aim of this study was to investigate whether milk fortified with folic acid enhances the folate status of humans and whether the presence of folate-binding proteins (FBP) in pasteurised milk affects the bioavailability of folic acid from fortified milk. In untreated and pasteurised milk, folate occurs bound to FBP, while FBP is (partly) denatured in ultra-high-temperature (UHT)-treated milk. The effect of FBP on folate bioavailability is still unclear. Design, subjects and setting Healthy, free-living subjects (n=69) aged 18-49 y participated in a 4-week double-blind, placebo-controlled dietary intervention study. Intervention In addition to a fully controlled diet, the subjects consumed each day 500 ml of pasteurised or UHT milk, either fortified or not with 200 g folic acid. Results Consumption of fortified milk increased folate concentrations in serum and in red blood cells (RBC) by 6.6-7.0 nmol/l (P
No effect of folic acid supplementation in the course of 1 year on heamostasis markers and C-reactive protein in older adults
Klerk, M. ; Durga, J. ; Schouten, E.G. ; Kluft, C. ; Kok, F.J. ; Verhoef, P. - \ 2005
Thrombosis and Haemostasis 94 (2005)1. - ISSN 0340-6245 - p. 96 - 100.
von-willebrand-factor - ischemic-heart-disease - plasminogen-activator inhibitor - homocysteine-lowering treatment - endothelial dysfunction - cardiovascular-disease - methylenetetrahydrofolate reductase - risk-factor - hyperhomocysteinaemic patients - myocardial-
Elevated homocysteine levels are associated with an increased cardiovascular disease (CVD) risk, but the underlying mechanism is still unclear. High homocysteine might affect the endothelium, and consequently lead to impaired haemostasis. In a randomized placebo controlled trial among 276 older adults with plasma total homocysteine concentrations above 13 mM at screening, we investigated the effect of homocysteine lowering by folic acid supplementation (0.8 mg/day) for 1 year on markers of endothelial function (vonWillebrand factor), coagulation (tissue factor, factor VIIa, fragments 1+2), and fibrinolysis (fibrin degradation products, tissue-type plasminogen activator), and inflammation (C-reactive protein). Despite a 24% reduction in plasma homocysteine concentration and four-fold increase in serum folate concentration in the folic acid group compared to the placebo group, there was no clear change in any of the haemostasis markers, nor CRP. Although homocysteine is associated with vascular disease risk in the general population,marked lowering of slightly elevated homocysteine concentrations by one-year folic acid supplementation does not influence haemostasis markers
Low concentrations of folate, not hyperhomocysteinemia, are associated with carotid intima-media thickness
Durga, J. ; Bots, M.L. ; Schouten, E.G. ; Kok, F.J. ; Verhoef, P. - \ 2005
Atherosclerosis 179 (2005)2. - ISSN 0021-9150 - p. 285 - 292.
stage renal-disease - methylenetetrahydrofolate reductase - plasma homocysteine - general-population - large arteries - heart-disease - risk - atherosclerosis - coronary - mutation
Aim: We examined whether total homocysteine, B vitamins and the 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C ¿ T polymorphism are related to common carotid intima-media thickness, a marker of atherosclerosis, and carotid distension, a marker of arterial stiffness. Methods: We used cross-sectional data from 819 individuals aged 50-70 years. B-mode ultrasound of the distal common carotid arteries was performed to determine maximum carotid intima-media thickness, mean carotid intima-media thickness and distension. Results: Carotid intima-media thickness and distension did not differ across homocysteine, serum folate, vitamin B6 and vitamin B12 quartiles or between MTHFR C677T genotype. Erythrocyte folate was independently associated with maximum carotid intima-media thickness (mean difference first versus third quartile, 0.03 mm, 95% CI 0.004-0.06 mm; first versus fourth quartile, 0.03 mm, 95% CI -0.002 to 0.06 mm). Further adjustment for homocysteine did not affect this association. Folate deficient subjects had greater maximum carotid intima-media thickness than those with high-normal folate concentrations (serum folate: mean difference 0.05 mm, 95% CI 0.01-0.08 mm; erythrocyte folate: mean difference 0.04 mm, 95% CI -0.03 to 0.11 mm). Conclusion: Low folate concentrations, independent of hyperhomocysteinemia, may promote atherogenesis. Our findings confirm the null association of homocysteine with carotid intima-media thickness observed in other population-based studies, suggesting that hyperhomocysteinemia does not perpetuate atherosclerosis or arterial stiffness
Coenzyme binding is beneficial for the stability of 4 hydroxyacetophenone monooxygenase
Heuvel, R.H.H. van den; Tahallah, N. ; Kamerbeek, N.M. ; Fraaije, M.W. ; Berkel, W.J.H. van; Janssen, D.B. ; Heck, A. - \ 2005
Journal of Biological Chemistry 280 (2005)37. - ISSN 0021-9258 - p. 32115 - 32121.
baeyer-villiger monooxygenases - ionization mass-spectrometry - vanillyl-alcohol oxidase - electrospray-ionization - escherichia-coli - methylenetetrahydrofolate reductase - cyclohexanone monooxygenase - synthetic applications - protein complexes - specificity
The NADPH-dependent dimeric flavoenzyme 4-hydroxyacetophenone monooxygenase (HAPMO) catalyzes Baeyer-Villiger oxidations of a wide range of ketones, thereby generating esters or lactones. In the current work, we probed HAPMO-coenzyme complexes present during the enzyme catalytic cycle with the aim to gain mechanistic insight. Moreover, we investigated the structural role of the nicotinamide coenzyme. For these studies, we used (i) wild type HAPMO, (ii) the R339A variant, which is active but has a low affinity toward NADPH, and (iii) the R440A variant, which is inactive but has a high affinity toward NADPH. Electrospray ionization mass spectrometry was used as the primary tool to directly observe noncovalent protein-coenzyme complexes in real time. These analyzes showed for the first time that the nicotinamide coenzyme remains bound to HAPMO during the entire catalytic cycle of the NADPH oxidase reaction. This may also have implications for other homologous Baeyer-Villiger monooxygenases. Together with the observations that NADP+ only weakly interacts with oxidized enzyme and that HAPMO is mainly in the reduced form during catalysis, we concluded that NADP+ interacts tightly with the reduced form of HAPMO. We also demonstrated that the association with the coenzyme is crucial for enzyme stability. The interaction with the coenzyme analog 3-aminopyridine adenine dinucleotide phosphate (AADP+) strongly enhanced the thermal stability of wild type HAPMO. This coenzyme-induced stabilization may also be important for related enzymes.
Folate bioavailibility: UK Food Standards Agency workshop report
Sanderson, P. ; McNulty, H.M. ; Mastroiacovo, P. ; McDowell, I.F.W. ; Melse, A. ; Finglas, P.M. ; Gregory III, J.F. - \ 2003
The British journal of nutrition 90 (2003)2. - ISSN 0007-1145 - p. 473 - 479.
neural-tube defects - glutamate carboxypeptidase-ii - cardiovascular-disease risk - framingham offspring cohort - randomized controlled trial - folic-acid - methylenetetrahydrofolate reductase - plasma homocysteine - 5,10-methylenetetrahydrofolate reductase - supp
The UK Food Standards Agency convened a group of expert scientists to review current research investigating folate bioavailability. The workshop aimed to overview current research and establish priorities for future research. Discrepancies were observed in the evidence base for folate bioavailability, especially with regard to the relative bioavailability of natural folates compared with folic acid. A substantial body of evidence shows folic acid to have superior bioavailability relative to food folates; however, the exact relative bioavailability still needs to be determined, and in particular with regard to mixed diets. The bioavailability of folate in a mixed diet is probably not a weighted average of that in the various foods consumed; thus the workshop considered that assessment of folate bioavailability of whole diets should be a high priority for future research.
Betaine supplementation lowers plasma homocysteine levels in healthy men and women
Steenge, G.R.S. ; Verhoef, P. ; Katan, M.B. - \ 2003
The Journal of Nutrition 133 (2003). - ISSN 0022-3166 - p. 1291 - 1295.
dose folic-acid - cardiovascular-disease - methylenetetrahydrofolate reductase - vascular-disease - risk factor - dietary betaine - methionine - methyltransferase - metabolism - pyridoxine
Elevated levels of plasma total homocysteine are associated with a higher risk of cardiovascular disease. Betaine and 5-methyltetrahydrofolate can remethylate homocysteine into methionine via independent reactions. We determined the effect of daily betaine supplementation, compared with both folic acid and placebo, on plasma concentrations of total homocysteine after an overnight fast and after methionine loading in men and women with mildly elevated homocysteine. Groups of twelve subjects ingested 6 g betaine, 800 jig folic acid with 6 g placebo or 6 g placebo each day for 6 wk. A methionine-loading test (i.e., ingestion Of 100 mg L-methionine/kg body mass) was performed before and after 6 wk of supplementation. Fasting plasma homocysteine decreased by 1.8 mumol/L (95% confidence interval [CI]: -3.6, 0.0, P <0.05) in the betaine group and by 2.7 mumol/L (95% CI: -4.5, -0.9, P <0.05) in the folic acid group. These changes are relative to the change in the placebo group, in which fasting plasma homocysteine rose by 0.5 mumol/L. Furthermore, betaine suppressed the total area under the plasma homocysteine-time curve after methionine loading by 221 mumol - 24 h/L (95% CI: -425, -16, P <0.05) compared with placebo, whereas folic acid had no effect. In conclusion, betaine appears to be highly effective in preventing a rise in plasma homocysteine concentration after methionine intake in subjects with mildly elevated homocysteine. It is not known whether this potential of betaine to "stabilize" circulating homocysteine concentrations lowers the risk of cardiovascular disease. J. Nutr. 133: 1291-1295, 2003.