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      Biomarkers of Nutrition for Development—Folate Review 1 2 3 4 5

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          Abstract

          The Biomarkers of Nutrition for Development (BOND) project is designed to provide evidence-based advice to anyone with an interest in the role of nutrition in health. Specifically, the BOND program provides state-of-the-art information and service with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect. To accomplish this objective, expert panels are recruited to evaluate the literature and to draft comprehensive reports on the current state of the art with regard to specific nutrient biology and available biomarkers for assessing nutrients in body tissues at the individual and population level. Phase I of the BOND project includes the evaluation of biomarkers for 6 nutrients: iodine, iron, zinc, folate, vitamin A, and vitamin B-12. This review represents the second in the series of reviews and covers all relevant aspects of folate biology and biomarkers. The article is organized to provide the reader with a full appreciation of folate’s history as a public health issue, its biology, and an overview of available biomarkers (serum folate, RBC folate, and plasma homocysteine concentrations) and their interpretation across a range of clinical and population-based uses. The article also includes a list of priority research needs for advancing the area of folate biomarkers related to nutritional health status and development.

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          Most cited references 307

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          Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression.

          Multiple, complex molecular events characterize cancer development and progression. Deciphering the molecular networks that distinguish organ-confined disease from metastatic disease may lead to the identification of critical biomarkers for cancer invasion and disease aggressiveness. Although gene and protein expression have been extensively profiled in human tumours, little is known about the global metabolomic alterations that characterize neoplastic progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we profiled more than 1,126 metabolites across 262 clinical samples related to prostate cancer (42 tissues and 110 each of urine and plasma). These unbiased metabolomic profiles were able to distinguish benign prostate, clinically localized prostate cancer and metastatic disease. Sarcosine, an N-methyl derivative of the amino acid glycine, was identified as a differential metabolite that was highly increased during prostate cancer progression to metastasis and can be detected non-invasively in urine. Sarcosine levels were also increased in invasive prostate cancer cell lines relative to benign prostate epithelial cells. Knockdown of glycine-N-methyl transferase, the enzyme that generates sarcosine from glycine, attenuated prostate cancer invasion. Addition of exogenous sarcosine or knockdown of the enzyme that leads to sarcosine degradation, sarcosine dehydrogenase, induced an invasive phenotype in benign prostate epithelial cells. Androgen receptor and the ERG gene fusion product coordinately regulate components of the sarcosine pathway. Here, by profiling the metabolomic alterations of prostate cancer progression, we reveal sarcosine as a potentially important metabolic intermediary of cancer cell invasion and aggressivity.
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            A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements.

            We report a method for studying global DNA methylation based on using bisulfite treatment of DNA and simultaneous PCR of multiple DNA repetitive elements, such as Alu elements and long interspersed nucleotide elements (LINE). The PCR product, which represents a pool of approximately 15 000 genomic loci, could be used for direct sequencing, selective restriction digestion or pyrosequencing, in order to quantitate DNA methylation. By restriction digestion or pyrosequencing, the assay was reproducible with a standard deviation of only 2% between assays. Using this method we found that almost two-thirds of the CpG methylation sites in Alu elements are mutated, but of the remaining methylation target sites, 87% were methylated. Due to the heavy methylation of repetitive elements, this assay was especially useful in detecting decreases in DNA methylation, and this assay was validated by examining cell lines treated with the methylation inhibitor 5-aza-2'deoxycytidine (DAC), where we found a 1-16% decrease in Alu element and 18-60% LINE methylation within 3 days of treatment. This method can be used as a surrogate marker of genome-wide methylation changes. In addition, it is less labor intensive and requires less DNA than previous methods of assessing global DNA methylation.
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              Prevention of neural-tube defects with folic acid in China. China-U.S. Collaborative Project for Neural Tube Defect Prevention.

              Periconceptional administration of folic acid can reduce a woman's risk of having a fetus or infant with a neural-tube defect. As part of a public health campaign conducted from 1993 to 1995 in an area of China with high rates of neural-tube defects (the northern region) and one with low rates (the southern region), we evaluated the outcomes of pregnancy in women who were asked to take a pill containing 400 microg of folic acid alone daily from the time of their premarital examination until the end of their first trimester of pregnancy. Among the fetuses or infants of 130,142 women who took folic acid at any time before or during pregnancy and 117,689 women who had not taken folic acid, we identified 102 and 173, respectively, with neural-tube defects. Among the fetuses or infants of women who registered before their last menstrual period and who did not take any folic acid, the rates of neural-tube defects were 4.8 per 1000 pregnancies of at least 20 weeks' gestation in the northern region and 1.0 per 1000 in the southern region. Among the fetuses or infants of the women with periconceptional use of folic acid, the rates were 1.0 per 1000 in the northern region and 0.6 per 1000 in the southern region. The greatest reduction in risk occurred among the fetuses or infants of a subgroup of women in the northern region with periconceptional use who took folic acid pills more than 80 percent of the time (reduction in risk, 85 percent as compared with the fetuses or infants of women who registered before their last menstrual period and who took no folic acid; 95 percent confidence interval, 62 to 94 percent) [corrected]. In the southern region the reduction in risk among the fetuses or infants of women with periconceptional use of folic acid was also significant (reduction in risk, 41 percent; 95 percent confidence interval, 3 to 64 percent). Periconceptional intake of 400 microg of folic acid daily can reduce the risk of neural-tube defects in areas with high rates of these defects and in areas with low rates.
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                Author and article information

                Journal
                J Nutr
                nutrition
                nutrition
                The Journal of Nutrition
                American Society for Nutrition
                0022-3166
                1541-6100
                July 2015
                3 June 2015
                3 June 2015
                : 145
                : 7
                : 1636S-1680S
                Affiliations
                [6 ]Department of Foods and Nutrition, University of Georgia, Athens, GA;
                [7 ]Division of Nutritional Sciences, Cornell University, Ithaca, NY;
                [8 ]Northern Ireland Centre for Food and Health, Biomedical Sciences Research Institute, University of Ulster, Londonderry, United Kingdom;
                [9 ]Genome Health Nutrigenomics Laboratory, Food, Nutrition, and Bioproducts Flagship, Commonwealth Scientific and Industrial Research Organization, Adelaide, Australia;
                [10 ]Food Science and Human Nutrition Department, University of Florida, Gainesville, FL;
                [11 ] Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD;
                [12 ]National Center for Environmental Health, CDC, Atlanta, GA;
                [13 ]Department of Clinical Science, Univeristy of Bergen, Bergen, Norway;
                [14 ]Institute of Molecular Medicine, Trinity College, Dublin, Ireland;
                [15 ]Department of Nutritional Sciences and Toxicology, University of California–Berkeley, Berkeley, CA;
                [16 ]National Center on Birth Defects and Developmental Disabilities, CDC, Atlanta, GA; and
                [17 ]Office of Dietary Supplements, NIH, Bethesda, MD
                Author notes
                [* ]To whom correspondence should be addressed. E-mail: raitend@ 123456mail.nih.gov (DJ Raiten), folate@ 123456uga.edu (LB Bailey).
                [1]

                Published in a supplement to The Journal of Nutrition. The Biomarkers of Nutrition for Development (BOND) project was developed by the nutrition program staff of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the NIH within the US Department of Health and Human Services (DHHS). The initial 6 nutrients selected, iodine, vitamin A, iron, zinc, folate, and vitamin B-12, were chosen for their high public health importance. Expert panels on each nutrient were constituted and charged with developing comprehensive reviews for publication in the BOND series. The BOND program received its core funding from the Bill & Melinda Gates Foundation, PepsiCo, the Division of Nutrition Research Coordination (DNRC, NIH), the Office of Dietary Supplements (ODS, NIH), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD, NIH). The Supplement Coordinators for this supplement were Daniel J Raiten (NICHD, NIH) and Lynn B Bailey (University of Georgia). Supplement Coordinators disclosures: no conflicts of interest. This supplement is the responsibility of the Guest Editor to whom the Editor of The Journal of Nutrition has delegated supervision of both technical conformity to the published regulations of The Journal of Nutrition and general oversight of the scientific merit of each article. The Guest Editor for this supplement was Kevin L Schalinske. Guest Editor disclosure: no conflicts of interest. Publication costs for this supplement were defrayed in part by the payment of page charges. This publication must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact. The opinions expressed in this publication are those of the authors and are not attributable to the sponsors or the publisher, Editor, or Editorial Board of The Journal of Nutrition.

                [2]

                The BOND project was funded in part by the Bill & Melinda Gates Foundation; PepsiCo; the Office of Dietary Supplements (ODS, NIH); the Division of Nutrition Research Coordination (DNRC, NIH); and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD, NIH). The Folate Review was written in response to an invitation from the NICHD of the NIH within the US Department of Health and Human Services (DHHS). This is a free access article, distributed under terms ( http://www.nutrition.org/publications/guidelines-and-policies/license/) that permit unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                [3]

                Author disclosures: LB Bailey, PJ Stover, H McNulty, MF Fenech, JF Gregory III, JL Mills, CM Pfeiffer, Z Fazili, M Zhang, PM Ueland, AM Molloy, MA Caudill, B Shane, RJ Berry, RL Bailey, DB Hausman, R Raghavan, and DJ Raiten, no conflicts of interest.

                [4]

                The content represents the views of the Folate Expert Panel and other invited contributors and does not necessarily represent the official views or positions of the NIH, the CDC/Agency for Toxic Substances and Disease Registry, or the DHHS. In addition, individual members of the expert panel may not endorse all statements in this report.

                [5]

                Supplemental Tables 1 and 2 are available from the ‘‘Online Supporting Material’’ link in the online posting of the article and from the same link in the online table of contents at http://jn.nutrition.org.

                Article
                206599
                10.3945/jn.114.206599
                4478945
                © 2015 American Society for Nutrition

                This is a free access article, distributed under terms ( http://www.nutrition.org/publications/guidelines-and-policies/license/) that permit unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Page count
                Pages: 45
                Categories
                Supplement: Biomarkers of Nutrition for Development (BOND) Expert Panel Reviews, Part 2

                Nutrition & Dietetics

                bond, folate biomarkers, serum folate, rbc folate, homocysteine

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