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Amanda M Henderson, Rika E Aleliunas, Su Peng Loh, Geok Lin Khor, Sarah Harvey-Leeson, Melissa B Glier, David D Kitts, Tim J Green, Angela M Devlin
Background: Folic acid fortification of grains is mandated in many countries to prevent neural tube defects. Concerns regarding excessive intakes of folic acid have been raised. A synthetic analog of the circulating form of folate, l-5-methyltetrahydrofolate (l-5-MTHF), may be a potential alternative. Objective: The objective of this study was to determine the effects of folic acid or l-5-MTHF supplementation on blood folate concentrations, methyl nutrient metabolites, and DNA methylation in women living in Malaysia, where there is no mandatory fortification policy...
June 1, 2018: Journal of Nutrition
Pankaj Bhatia, Nirmal Singh
Homocysteine (Hcy) is a nonproteogenic sulfur containing amino acid derived from dietary methionine through demethylation. Homocysteine can be re-methylated to methionine [precursor of S-adenosylmethionine (SAM)] via the re-methylation or 5-methyltetrahydrofolate pathway or undergoes transsulfuration to form cysteine by the action of metabolic enzymes and cofactors. Impaired metabolism due to genetic alteration in metabolic enzymes (methionine synthase, methyltetrahydrofolate reductase (MTHFR), cystathionine β-synthase (CβS), and cystathionine-γ-lyase (CγL) or deficiency in cofactors (vitamin B6 , B12 , folate) may lead to acquired metabolic anomaly known as hyperhomocysteinemia...
December 2015: Fundamental & Clinical Pharmacology
Irene Pusceddu, Markus Herrmann, Susanne H Kirsch, Christian Werner, Ulrich Hübner, Marion Bodis, Ulrich Laufs, Stefan Wagenpfeil, Jürgen Geisel, Wolfgang Herrmann
PURPOSE: Deficiencies of folate, vitamins B12 and D are common age-related conditions. Vitamin B12 and folate are necessary for DNA methylation. Telomeres appear to be regulated by DNA methylation. Here, we study the effect of B vitamins supplementation on telomere length and global DNA methylation in a prospective study. METHODS: In total, 60 elderly subjects were supplemented for 1 year with either vitamin B12, B6, folate, vitamin D and calcium (group A n = 31) or only vitamin D and calcium (group B n = 29)...
August 2016: European Journal of Nutrition
Ting-Yuan David Cheng, Karen W Makar, Marian L Neuhouser, Joshua W Miller, Xiaoling Song, Elissa C Brown, Shirley A A Beresford, Yingye Zheng, Elizabeth M Poole, Rachel L Galbraith, David J Duggan, Nina Habermann, Lynn B Bailey, David R Maneval, Marie A Caudill, Adetunji T Toriola, Ralph Green, Cornelia M Ulrich
BACKGROUND: Investigations of folate-mediated one-carbon metabolism (FOCM) genes and gene-nutrient interactions with respect to colorectal cancer (CRC) risk are limited to candidate polymorphisms and dietary folate. This study comprehensively investigated associations between genetic variants in FOCM and CRC risk and whether the FOCM nutrient status modified these associations. METHODS: Two hundred eighty-eight candidate and tagging single-nucleotide polymorphisms (SNPs) in 30 FOCM genes were genotyped for 821 incident CRC case-control matched pairs in the Women's Health Initiative Observational Study cohort...
October 15, 2015: Cancer
G Szabó, L Lazar, B Nagy, J Rigo
INTRODUCTION: One-carbon cycle is involved in two essential physiological processes: The synthesis of purins and pyrimidines required for DNA synthesis and repair. The other is the methylation with the methionine cycle. These one-carbon groups are served by the tetrahydrofolate and the S-adenosylmethionine. Deficiencies of the folate, or other abnormalities within the methionine pathway lead to elevated homocysteine levels. These disorders have been implicated in placental diseases. Earlier studies have shown that homocysteine levels are elevated by patients with severe pre-eclampsia than by healthy pregnant normotensive women...
July 2012: Pregnancy Hypertension
A Torres, S A Newton, B Crompton, A Borzutzky, E J Neufeld, L Notarangelo, G T Berry
Hereditary folate malabsorption is characterized by folate deficiency with impaired folate transport into the central nervous system (CNS). This disease is characterized by megaloblastic anemia of early appearance, combined immunodeficiency, seizures, and cognitive impairment. The anemia and immunologic disease are responsive but neurological signs are refractory to folic-acid treatment. We report a 7-year-old girl who has congenital folate deficiency and SLC46A1 gene mutation who is unable to transport folate from her gut to the circulatory system and consequently from the blood to the cerebrospinal fluid (CSF)...
2015: JIMD Reports
Christine M Pfeiffer, Maya R Sternberg, Zia Fazili, David A Lacher, Mindy Zhang, Clifford L Johnson, Heather C Hamner, Regan L Bailey, Jeanne I Rader, Sedigheh Yamini, R J Berry, Elizabeth A Yetley
Serum and erythrocyte (RBC) total folate are indicators of folate status. No nationally representative population data exist for folate forms. We measured the serum folate forms (5-methyltetrahydrofolate (5-methylTHF), unmetabolised folic acid (UMFA), non-methyl folate (sum of tetrahydrofolate (THF), 5-formyltetrahydrofolate (5-formylTHF), 5,10-methenyltetrahydrofolate (5,10-methenylTHF)) and MeFox (5-methylTHF oxidation product)) by HPLC-MS/MS and RBC total folate by microbiologic assay in US population ≥ 1 year (n approximately 7500) participating in the National Health and Nutrition Examination Survey 2011-2...
June 28, 2015: British Journal of Nutrition
Pasquale Ambrosino, Roberta Lupoli, Alessandro Di Minno, Assunta Nardo, Emiliana Marrone, Valentina Lupoli, Alessandra Scaravilli, Emma Mitidieri, Antonella Tufano, Matteo Nicola Dario Di Minno
Folic acid supplementation is the mainstay treatment of hyperhomocysteinemia (HHcy). However, no recommendations are currently available in regard to the optimal replacement therapy. Therefore, this prospective study hypothesized that a cyclic schedule (1 month of therapy followed by 2 months of withdrawal) of 5-methyltetrahydrofolate (5-MTHF) would reduce plasma levels of fasting total homocysteine (tHcy) in patients with mild/moderate HHcy. Patients with a new diagnosis of mild/moderate HHcy were evaluated for the methylenetetrahydrofolate reductase genotype and the presence of major features of metabolic syndrome...
June 2015: Nutrition Research
Anna E Stanhewicz, Lacy M Alexander, W Larry Kenney
Older adults have reduced vascular endothelial function, evidenced by attenuated nitric oxide (NO)-dependent cutaneous vasodilatation. Folic acid and its metabolite, 5-methyltetrahydrofolate (5-MTHF), are reported to improve vessel function. We hypothesized that (i) local 5-MTHF administration and (ii) chronic folic acid supplementation would improve cutaneous microvascular function in ageing through NO-dependent mechanisms. There were two separate studies in which there were 11 young (Y: 22 ± 1 years) and 11 older (O: 71 ± 3 years) participants...
July 2015: Clinical Science (1979-)
Christine M Pfeiffer, Maya R Sternberg, Zia Fazili, Elizabeth A Yetley, David A Lacher, Regan L Bailey, Clifford L Johnson
BACKGROUND: Serum total folate consists mainly of 5-methyltetrahydrofolate (5-methylTHF). Unmetabolized folic acid (UMFA) may occur in persons consuming folic acid-fortified foods or supplements. OBJECTIVES: We describe serum 5-methylTHF and UMFA concentrations in the US population ≥1 y of age by demographic variables and fasting time, stratified by folic acid-containing dietary supplement use. We also evaluate factors associated with UMFA concentrations >1 nmol/L...
March 2015: Journal of Nutrition
Stephen Tomiuk, Yazheng Liu, Tim J Green, Maria J King, Paul M Finglas, David D Kitts
Our aim was to protect l-5-methyltetrahydrofolic acid (L-5-MTHF) from degradation throughout the baking and storage of a fortified white bread using microencapsulation. L-5-MTHF, with or without sodium ascorbate (ASC), was microencapsulated using skim milk powder (SMP) as the coating agent. Recoveries of L-5-MTHF in spray-dried materials were greater than 95 ± 5%. Microencapsulated L-5-MTHF was completely released from the skim milk coating material in simulated gastric fluid within the first 10 min at 37°C...
July 15, 2012: Food Chemistry
Zia Fazili, Maya R Sternberg, Neelima Paladugula, Ralph D Whitehead, Huiping Chen, Christine M Pfeiffer
BACKGROUND: Maintaining folate stability during sample handling is important, yet challenging. OBJECTIVE: We investigated the effects of suboptimal preanalytical conditions on serum folate stability. METHODS: By using an HPLC-tandem MS method we measured folates [5-methyltetrahydrofolate (5-methylTHF), folic acid, MeFox (5-methylTHF oxidation product, pyrazino-s-triazine derivative of 4α-hydroxy-5-methylTHF), and other minor folate forms at or below the limit of detection] in human serum exposed to suboptimal conditions...
November 2014: Journal of Nutrition
Alanna Lakoff, Zia Fazili, Susanne Aufreiter, Christine M Pfeiffer, Bairbie Connolly, Jesse F Gregory, Paul B Pencharz, Deborah L O'Connor
BACKGROUND: Folate intakes that do not meet or greatly exceed requirements may be associated with negative health outcomes. A better understanding of contributors that influence the input side will help establish dietary guidance that ensures health benefits without associated risks. Colonic microbiota produce large quantities of folate, and [(13)C5]5-formyltetrahydrofolate infused during colonoscopy is absorbed. However, it is unclear if significant quantities of folate are absorbed in an intact microbiome...
November 2014: American Journal of Clinical Nutrition
Yazheng Liu, Timothy J Green, David D Kitts
Here we report on the comparative stability of free and microencapsulated L-5-methyltetrahydrofolate (L-5-MTHF) with free folic acid (FA) when exposed to thermal cooking conditions that are common to noodle making. Fortifying noodle flour with free L-5-MTHF produced the greatest loss of the vitamin when noodles were cooked. In contrast, the percentage recovery of microencapsulated L-5-MTHF in both fresh and cooked noodles was not significantly different to noodles that were similarly processed with fortified FA...
March 15, 2015: Food Chemistry
Faith Pangilinan, Anne M Molloy, James L Mills, James F Troendle, Anne Parle-McDermott, Denise M Kay, Marilyn L Browne, Emily C McGrath, Hatice Ozel Abaan, Marie Sutton, Peadar N Kirke, Michele Caggana, Barry Shane, John M Scott, Lawrence C Brody
BACKGROUND: Neural tube defects (NTDs), which are among the most common congenital malformations, are influenced by environmental and genetic factors. Low maternal folate is the strongest known contributing factor, making variants in genes in the folate metabolic pathway attractive candidates for NTD risk. Multiple studies have identified nominally significant allelic associations with NTDs. We tested whether associations detected in a large Irish cohort could be replicated in an independent population...
October 8, 2014: BMC Medical Genetics
Susanne H Kirsch, Wolfgang Herrmann, Vera Kruse, Rudolf Eckert, Stefan Gräber, Jürgen Geisel, Rima Obeid
BACKGROUND: We aimed to study the effect of long-term supplementation of B-vitamins on folate forms in serum and whole blood (WB) in elderly German subjects. METHODS: 59 participants (mean age 67 years) were randomized to daily receive either vitamin D3 (1200 IU), folic acid (500 μg), vitamin B12 (500 μg), vitamin B6 (50 mg), and calcium carbonate (456 mg) or vitamin D3 plus calcium carbonate. Serum and WB folate forms were measured before and after 6 and 12 months...
February 2015: Clinical Chemistry and Laboratory Medicine: CCLM
Sunhyun Park, Min-Jeong Kim, Jiyoung Hong, Hyo-Jin Kim, Sung-Hun Yi, Myung-Ki Lee
This study was executed to develop probiotics producing S-adenosyl-L-methionine (SAMe), a methyl group donor in the 5-methyltetrahydrofolate methylation reaction in animal cells. SAMe is an essential substance in the synthesis, activation, and metabolism of hormones, neurotransmitters, nucleic acids, phospholipids, and cell membranes of animals. SAMe is also known as a nutritional supplement for improving human brain function. In this study, SAMe-producing strains were identified in six kinds of Cheonggukjang, and strains with excellent SAMe production were identified, with one strain in the Enterococcus genus and six strains in the Bacillus genus...
November 2014: Journal of Medicinal Food
L Wang, C Wang, T T Ge, J J Wang, T K Liu, X L Hou, Y Li
In Brassicaceae, a self-incompatibility (SI) system mediates pollen-pistil interactions. Self-pollen could be recognized and rejected by incompatible pistils. Several components involved in the SI response have been determined, including S-locus receptor kinase (SRK), S-locus cysteine-rich protein/S-locus protein 11, and arm repeat-containing protein 1 (ARC1). However, the components involved in the SI system of Brassicaceae are not fully understood. Here, we detected expression patterns of 24 SI-related genes in non-heading Chinese cabbage (Brassica campestris ssp chinensis Makino) after compatible and incompatible pollination, and potential interaction relationships of these genes were predicted...
2014: Genetics and Molecular Research: GMR
Brenda A Hartman, Zia Fazili, Christine M Pfeiffer, Deborah L O'Connor
It is not known whether folate metabolism is altered during pregnancy to support increased DNA and RNA biosynthesis. By using a state-of-the-art LC tandem mass spectrometry technique, the aim of this study was to investigate differences in RBC folate forms between pregnant and nonpregnant women and between nonpregnant women consuming different concentrations of supplemental folic acid. Forms of folate in RBCs were used to explore potential shifts in folate metabolism during early erythropoiesis. Total RBC folate and folate forms [tetrahydrofolate; 5-methyltetrahydrofolate (5-methyl-THF); 4α-hydroxy-5-methyl-tetrahydrofolate (an oxidation product of 5-methyl-THF); 5-formyl-tetrahydrofolate; and 5,10-methenyl-tetrahydrofolate] were measured in 4 groups of women (n = 26): pregnant women (PW) (30-36 wk of gestation) consuming 1 mg/d of folic acid, and nonpregnant women consuming 0 mg/d (NPW-0), 1 mg/d (NPW-1), and 5 mg/d (NPW-5) folic acid...
September 2014: Journal of Nutrition
Tyler Duellman, Christopher L Warren, Jon Matsumura, Jay Yang
BACKGROUND: The natural history of abdominal aortic aneurysms (AAAs) suggests that some remain slow in growth rate whereas many develop a more accelerated growth rate and reach a threshold for intervention. We hypothesized that different mechanisms are responsible for AAAs that remain slow growing and never become actionable vs the aggressive AAAs that require intervention and may be reflected by distinct associations with genetic polymorphisms. METHODS: AAA growth rate was determined from serial imaging data in 168 control and 141 AAA patients with ultrasound or computed tomography imaging studies covering ∼5 years...
September 2014: Journal of Vascular Surgery
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