Progress 10/15/08 to 10/14/14
Outputs
Target Audience: Other researchers interested in this field of research were reached through presentations (poster sessions) at professional meetings and abstract publications. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided? Professional development: Attendance at the 2014 Experimental Biology meeting. This research provided the opportunity for a graduate student at one of the collaborating institutions to learn how to conduct research. It also provided undergraduate students at that instituion with the opportunity to assist with conducting a human subject research. How have the results been disseminated to communities of interest? Three poster presentations were presented at the 2014 Experimental Biology meeting, and the abstracts from each of these presentations were published in the FASEB Journal. A manuscript was submitted for publication to Plos One. The manuscript is currently under review. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
Objective 1: To investigate the relationship between dietary intake patterns and indices of vitamin B12 and folate status. To investigate whether the response to folic acid intake varies as a function of body weight, we examined the response of normal weight vs obese women to a single acute pharmacological dose of folic acid. This was the first study to examine the pharmacokinetic response in normal vs obese women to a level of folic acid intake consistent with the amount currently recommended for NTD risk reduction. Our data showed that the overall serum folate response was lower in obese vs normal weight women, which suggests that folate distribution is affected by obesity. If further research supports this finding, it would suggest the need for a BMI-adjusted folic acid intake recommendation for women of reproductive potential. This could result in an important strategy for reducing NTD risk among overweight/obese women who comprise more than 50% of women of reproductive potential. To investigate the influence of obesity on chronic folic acid supplementation, normal weight and obese women of childbearing age received a daily oral supplement containing 800 micrograms of folic acid for 8 weeks. There was no significant difference in the increase from baseline to 4 weeks between the groups; however, there was a plateau in the serum folate concentration from 4 to 8 weeks in the obese compared to the normal weight women. The lower baseline folate concentration and a response to chronic folic acid supplementation that appears to be saturable in the obese compared to the normal weight women provides additional evidence of a negative impact of obesity on folate metabolism/distribution and provide support for the concept of establishing a recommended intake for folic acid adjusted for BMI. Analysis of samples from women and children participating in the Guatemala National Maternal and Child Health Survey and the Belize National Survey on Micronutrient Biomarkers among Women of Reproductive Age and Children Study revealed that the percentage of women and children with deficient folate status was extremely low. Because the folate content of the traditional Belizean and Guatemalan diets is low, these data suggest that Belizean and Guatemalan women and children are consuming adequate amounts of folate from supplemental sources or from fortified foods imported from other countries. The data from our research team will be used by the Belize Ministry of Health to make policy decisions. Our research investigating the frequency of seafood consumption and vitamin B12 intake and status showed that seafood was the greatest contributor to vitamin B12 intake among nonvegetarians, and intake comparisons based on frequency of seafood consumption revealed that frequent seafood consumers had higher vitamin B12 intakes. These findings suggest that modest seafood intake contributes to maintaining normal B12 status. These findings have implications for seafood industry professionals who may want to highlight the contribution of seafood to vitamin B12 intake and status, and to registered dietitians who work with clients/patients who need to improve their vitamin B12 status or who are searching for a natural, high quality source of this important nutrient. Objective 2: To investigate the dietary vitamin B12 intake level consistent with maintenance of normal vitamin B12 status. Our collaborative research project investigating the dietary vitamin B12 intake level consistent with maintenance of normal vitamin B12 status suggests that the current recommended dietary allowance (RDA) for this nutrient is inadequate, at least for the population between 18 and 50 years of age. Our findings are likely to be considered the next time the RDA for this nutrient is revised. Objective 3: To examine nutrient-genome interactions in at-risk population subgroups. To investigate the influence of obesity on chronic folic acid (FA) supplementation, normal weight and obese women of childbearing age received a daily oral supplement containing 800 micrograms of folic acid for 8 weeks. Serum folate concentration and DNA methylation were assessed at baseline and after 4 and 8 weeks of supplementation. Only a small portion of CpG sites changed their DNA methylation profile in NTD- and folate pathway-related genes (i.e., 2.7% and 4.8% of total CpG sites in normal weight and obese, respectively). The DNA methylation response profile was different between the groups such that only 4 CpG sites (0.2%) responded in both NW and OB groups. Gene ontology analysis revealed 61BPs from 91 selected genes; 5 of the 61BPs responded to FA supplementation in normal weight subjects only, including neural tube closure, while 13 of the 61BPs responded in obese subjects only, including folate metabolism-related processes.
Publications
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2014
Citation:
Kauwell GPA, Caudill M, Hausman DB, Park HJ, Shade DC, Sokolow A, Malysheva O, Lewis RD, Bailey LB. Serum folate and whole blood global DNA methylation response to chronic folic acid supplementation in normal weight and obese women of child-bearing age. FASEB J April 2014 28:817.2 Also presented as a poster at the 2014 Experimental Biology Meeting in San Diego, CA on April 28, 2014. NIFA support acknowledged on the poster.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2014
Citation:
Shade D, Park HJ, Hausman D, Hohos N, Meagher R, Kauwell G, Smith A, Bailey L. Genome-wide DNA methylation in whole blood and CD16+ cells in response to chronic folic acid supplementation in women of child-bearing age (817.1) FASEB J April 2014 28:817.1 Also presented as a poster at the 2014 Experimental Biology Meeting in San Diego, CA on April 28, 2014. NIFA support acknowledged on the poster.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2014
Citation:
Park HJ, Shade D, Hausman D, Hohos N, Meagher R, Kauwell G, Smith A, Bailey L. Gene-specific changes in DNA methylation in response to chronic folic acid supplementation in normal weight and obese women of child-bearing age (817.3) FASEB J April 2014 28:817.3 Also presented as a poster at the 2014 Experimental Biology Meeting in San Diego, CA on April 28, 2014. NIFA support acknowledged on the poster.
- Type:
Journal Articles
Status:
Submitted
Year Published:
2015
Citation:
Shade DC, Park HJ, Hausman D, Hobos N, Meagher R, Kauwell GPA, Lewis RD, Smith A, Bailey L. DNA methylation changes in whole blood and CD16+ neutrophils in response to chronic folic acid supplementation in women of childbearing age. PLOS ONE. Manuscript number: PONE-D-14-36104; received August 11, 2014.
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Progress 10/01/12 to 09/30/13
Outputs
Target Audience:
Nothing Reported
Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided? This research provided the opportunity for a graduate student at my collaborating institution to learn how to conduct research. It also provided undergraduate students at that institution with the opportunity to assist with conducting a human subject study. How have the results been disseminated to communities of interest? A paper was published in the International Journal of Obesity, a poster session was presented at the Southern Translational Education and Research Conference and an oral presentation was give at the Experimental Biology meeting. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
Folate and vitamin B12 are vitamins with important health implications. Impaired folate/vitamin B12 status has been associated with increased risk for neural tube birth defects, chronic disease risk and neurological and cognitive dysfunction. More research is needed on which to base folate and vitamin B12 intake recommendations with the goal of reducing the health risks associated with inadequate intake or changes in the way the body handles these nutrients, some of which may bedue to genetic variation. In the US, neural tube defects (NTDs) are one of the most serious and debilitating birth defects. The lifetime medical costs associated with treating an NTD exceed $635,000. Therefore, NTD risk reduction represents an opportunity for improving pregnancy outcome, as well as reducing health care costs. The importance of periconceptional intake of folic acid and maternal folate status during the early weeks of gestation as it relates to development of the fetal neural tube has been well-established.Interestingly, greater adiposity has been associated with a higher risk for having a neural tube defect (NTD)-affected pregnancy, and an inverse relationship has been observed between body mass index (BMI) and folate status. Consequently, it is possible thatadiposity impairs folate status, which subsequently puts obese women at higherrisk for having an NTD-affected pregnancy. The current folic acid intake recommendationfor NTD risk reduction is the same for all women of reproductive potential irrespective of body weight, but our data suggest the possibility that folate requirements vary as a function of body weight.If future research provides sufficient evidence to support this idea, establishing a BMI-adjusted folic acid intake recommendation may ultimately impact public health by reducing NTD births among obese women. Objective 1: To investigate the relationship between dietary intake patterns and indices of vitamin B12 and folate status. To investigatewhetherthe response to folic acidintakevaries as a function ofbody weight,weexamined the responseof normal weight(BMI 18.5-24.9; n=16)vs obese women (BMI > or equal to 30; n=16)to a single acute pharmacological dose of folic acid (i.e., 400 micrograms). Blood samples were collected at 0.5, 1, 1.5, 2, 2.5, and hourly thereafter up to 10 hours after administering an oral dose of400 micrograms of folic acid.The blood samples were analyzed for serum and red blood cell folate concentrations, the former of which was used to generate area-under-the-curve (AUC) andmaximum response and peak time to concentration. Obese women had different overall serum responses to folic acid, with the AUC for the absorption phase and peak serum folate concentrations being lower in obese vs. normal weight women. This is the first study to examine thepharmacokinetic response in normal vs obese womento a level of folic acid intake consistent with the amount currently recommended for NTD risk reduction.Our data showed that the overall serum folate response was lower in obese vs normal weight women, suggesting that folate distribution is affected by obesity.If further research supports this finding, it wouldsuggest the need fora BMI-adjustedfolic acid intake recommendation for women of reproductive potential.This could result in an important strategy for reducing NTD risk among overweight/obese women who comprise more than 50% of women of reproductive potential. As an extension of this study, we conducted a follow up study to investigate the influence of obesity on chronic folic acid supplementation. In this study, normal weight (n=13) and obese (n=7) women of childbearing age received a daily oral supplement containing 800 micrograms of folic acid for 8 weeks. Serum folate concentration was measured at baseline, 4 and 8 weeks. At baseline, serum folate concentration was lower in obese vs normal weight women. There was no significant difference in the increase from baseline to 4 weeks between the groups; however, there wasa plateau in the serum folate concentration from 4 to 8 weeks in the obese compared to the normal weight women. The lower baseline folate concentration anda response to chronic folic acid supplementation that appears to be saturable in the obese compared to the normal weight women provides additional evidence of a negative impact of obesity on folate metabolism/distribution and provide support for the concept of establishing a recommended intake for folic acid adjusted for BMI. Objective 2: To investigate the dietary vitamin B12 intake level consistent with maintenance of normal vitamin B12 status. No projects related to this objective were undertaken during this reporting period. Objective 3: To examine nutrient-genome interactions in at-risk population subgroups. As described above,we conducted a follow up study to investigate the influence of obesity on chronic folic acid supplementation. In this study, normal weight (n=13) and obese (n=7) women of childbearing age received a daily oral supplement containing 800 micrograms of folic acid for 8 weeks. Serum folate concentration andDNA methylation were assessed at baseline and after 4 and 8 weeks of supplementation. The DNA methylation analyses were not completed prior to the end of this reporting period. The results from this aspect of our research will be included in next year's report.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2013
Citation:
da Silva VR, Hausman DB, Kauwell GP, Sokolow A, Tackett RL, Rathbun SL, Bailey LB. Obesity affects short-term folate pharmacokinetics in women of childbearing age. Int J Obes 2013; 1-3. (2013 Apr 9. doi: 10.1038/ijo.2013.41. Epub ahead of print)
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2013
Citation:
Shade DC, Park HJ, Hausman DB, Kauwell GPA, Sokolow A, Bailey LB. 2013. Obesity impacts the serum response to chronic folic acid supplementation in women of child-bearing age.Southern Translational Education and Research Conference, Augusta, GA, September 27, 2013.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2013
Citation:
da Silva VR, Hausman DB, Kauwell GP, Sokolow A, Tackett RL, Rathbun SL, Bailey LB. Obesity affects short-term folate pharmacokinetics in women of childbearing age. Experimental Biology, Boston, MA, April 22, 2013.
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Progress 10/01/11 to 09/30/12
Outputs
OUTPUTS: As part of our ongoing research collaboration with the Belize Ministry of Health, samples from Belizean children between the ages of 6 and 59 months and women of reproductive potential were analyzed for plasma folate and red blood cell (RBC) folate concentrations using the microbiological assay following the procedures established by the Centers for Disease Control and Prevention (CDC), which were adapted from the method of O'Broin et al. (1992). This study was undertaken to assess the magnitude of vitamin B12 (already completed) and folate deficiency in Belizean women and children as a basis for micronutrient intervention programs. A total of 4075 samples were analyzed: 1011 plasma samples from children and 1026 samples from women for analysis of plasma folate, and 1014 and 1024 whole blood samples from children and women, respectively, for analysis of red blood cell folate. Dissemination: The data from analysis of serum and RBC folate samples for Belizean women and children and a technical report were sent to the CDC and the Belize Ministry of Health. A manuscript for a refereed journal is in progress. An abstract summarizing our earlier work in Honduras and China was accepted for presentation at the American Society of Human Genetics. PARTICIPANTS: Dr. Gail P. A. Kauwell, PI Belizean studies, directed the development and adaptation of the folate analytical methodology; oversaw daily operation of sample analysis; supervised the collection, organization and analysis of data; participated in conference calls to report progress; co-wrote proposals/contracts for new funding; completed renewal paperwork for continuation of approved projects; oversaw budgetary issues to ensure sufficient funding for the project; wrote final report including description of analytical work and presentation of data for all collaborators. Dr. Kauwell collaborated on all aspects of other projects described above. Dr. Lynn B. Bailey, Co-PI Belizean study: communicated with Dr. Kauwell regarding sample analysis; co-wrote the proposals/contracts for funding; communicated with collaborators regarding plans for dissemination of research data including refereed publications. Nicte Ramirez, Foundation of the Institute of Nutrition for Central America and Panama (FANCAP): Guatemalan collaborator with whom the contracts were negotiated and to whom the data were submitted. She communicated with our research team about funding, execution of contracts, shipment of samples, and data evaluation. Natalia Largaespada Beer, Belize Ministry of Health Collaborator: primary contact in Belize for the study. Carmen Sanchez, CDC Collaborator in Belize: provided feedback on blood drawing/processing procedures; scheduled workshop at which members of our research team demonstrated techniques for processing samples shipped to our lab. Dr. Jorge Rosenthal, CDC/CCHP/NCBDDD: served as a collaborator for research being conducted in Honduras, Guatemala, and Belize; worked as a liaison with our research team and collaborators with the ministries of health and funding agencies in the respective countries; participated in conference calls with our research team and other collaborators at CDC and in Central America. Dr. Krista Crider, CDC/CCHP/NCBDDD: served as a project consultant for the Honduras study. Andrew Sokolow, Biological Scientist: conducted laboratory analysis of samples. David R. Maneval, Research Coordinator: support scientist. CDC provided funding for some aspects of the research plan. FANCAP provided funding for the Guatemalan study; partnered with our research team to design and implement the study. Belize Ministry of Health provided funding for Belize study; partnered with our research team to design and implement the study. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
It has been reported that children and women of reproductive age in Belize suffer from anemia and other adverse health-related effects of B-vitamin deficiencies. The Ministries of Health in Central America and the Caribean region were provided with funding from national and international agencies to assess baseline intake and blood concentrations of micronutrients. The purpose of the proposed population-based nutrient assessment studies is to provide the basis for nutrient intervention programs such as targeted supplementation and/or fortification of staple foods. Analysis of samples from women (n= 1026 serum samples; 1024 RBC samples) and children (n= 1011 serum samples; 1014 RBC samples) participating in the Belize National Survey on Micronutrient Biomarkers among Women of Reproductive Age and Children Study revealed that unlike our findings for vitamin B12 status, the percentage of women and children with deficient folate status was extremely low. These findings are similar to our findings in Guatemala, where only a very small percentage of women and children had suboptimal folate status. Because the folate content of the traditional Belizean diet is low, these data suggest that Belizean women and children are consuming adequate amounts of folate from supplemental sources or from fortified foods imported from other countries. The data from our research team will be used by the Belize Ministry of Health to make policy decisions. Plans for manuscript preparation in conjunction with investigators at the CDC and collaborators at the Belize Ministry of Health are in progress.
Publications
- Crider KS, Maneval DR, Dowling NF, Kauwell GPA, Ling H, Zhu L, Bailey LB, Berry RJ. 2012. Variants in one-carbon metabolism and blood folate, homocysteine and B12 deficiency in a population-based study. Electronic conference proceedigs (abstract), American Society of Human Genetics, San Francisco, CA, November, 2012.
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Progress 12/09/10 to 12/09/11
Outputs
OUTPUTS: Samples from Guatemalan children between the ages of 6 and 59 months were analyzed for vitamin B12 concentrations (N=1265) using electro-chemiluminescence immunoassay (ECLIA) and for red blood cell folate concentrations (N=1265) using the microbiological assay as part of our ongoing research collaboration with FANCAP. In the spring of 2011, members of our research lab traveled to Belize to demonstrate state-of-the-art techniques for blood collection, processing, and handling under field conditions in preparation for obtaining samples from individuals who agreed to participate in the Belize National Survey on Micronutrient Biomarkers among Women of Reproductive Age and Children study. This study is designed to assess the magnitude of folate and vitamin B12 deficiency in Belize as a basis for micronutrient intervention programs. A total of 1012 plasma samples from children and 1026 samples from women were collected and shipped to us for analysis of vitamin B12; and 1011 and 1026 plasma samples from children and women, respectively, were shipped to us for analysis of plasma folate; and1014 and 1024 whole blood samples from children and women, respectively, were shipped to us for analysis of red blood cell folate. All 2038 samples designated for vitamin B12 analysis have been completed. We are in the process of analyzing the whole blood folate samples and expect to complete them in January 2012. We expect to start analyzing the sample for serum folate in late January 2012, and complete them in March 2012, with a report to follow. Dissemination: The data from the vitamin B12 Guatemalan sample analysis and a technical report were submitted to the CDC and FANCAP in Guatemala. A manuscript for a peer-reviewed journal is in progress. The data from the vitamin B12 Belizean sample analysis and a technical report were to the CDC and the Belize Ministry of Health. An abstract summarizing our earlier work in Honduras was accepted for presentation at the International Congress of Human Genetics. PARTICIPANTS: Dr. Gail P. A. Kauwell, Co-PI Guatemalan studies, directed the development and adaptation of the folate analytical methodology; oversaw daily operation of samples analysis; supervised the collection, organization and analysis of data; participated in conference calls to report progress and to make plans for future studies; co-wrote proposals/contracts for new funding; completed renewal paperwork for continuation of approved projects; oversaw budgetary issues to ensure sufficient funding for the project; wrote final report including description of analytical work and presentation of data for all collaborators. Dr. Kauwell collaborated on all aspects of other projects described above. Dr. Lynn B. Bailey, Co-PI Guatemalan study: communicated with Dr. Kauwell regarding sample analysis; reviewed data; provided input on decisions regarding samples to be reanalyzed; co-wrote the proposals/contracts for funding; communicated with collaborators regarding plans for dissemination of research data including peer-reviewed publication; served as a liaison between research staff working under her supervision and research staff working under Dr. Kauwell's supervision. David R. Maneval, Research Coordinator: support scientist for all aspects of the research program described above. Nicte Ramirez, Foundation of the Institute of Nutrition for Central America and Panama (FANCAP): Guatemalan collaborator with whom the contracts were negotiated and to whom the data were submitted. She communicated with our research team about funding, execution of contracts, shipment of samples, and data evaluation. Natalia Largaespada Beer, Belize Ministry of Health Collaborator: primary contact in Belize for the initiation of the study. Carmen Sanchez, CDC Collaborator in Belize: provided feedback on blood drawing/processing procedures; scheduled workshop at which members of our research team will demonstrate techniques for processing samples to be shipped to our lab. Dr. Jorge Rosenthal, CDC/CCHP/NCBDDD: served as a collaborator for research being conducted in Honduras, Guatemala, and Belize; worked as a liaison with our research team and collaborators with the ministries of health and funding agencies in the respective countries; participated in conference calls with our research team and other collaborators at CDC and in Central America. Dr. Krista Crider, CDC/CCHP/NCBDDD: served as a project consultant for the Honduras study. CDC provided funding for some aspects of the research plan. FANCAP provided funding for the Guatemalan study; partnered with our research team to design and implement the study. Belize Ministry of Health provided funding for Belize study; partnered with our research team to design and implement the study. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
It has been reported that children and women of reproductive age in Guatemala and Belize suffer from anemia and other adverse health-related effects of B-vitamin deficiencies. The Ministries of Health in Central America and the Caribean region were provided funding by national and international agencies to assess baseline intake and blood concentrations of micronutrients. The purpose of the proposed population-based nutrient assessment studies is to provide the basis for nutrient intervention programs such as targeted supplementation and/or fortification of staple foods. Our data from the analysis of ~1265 samples of Guatemalan children participating in the Guatemala National Maternal and Child Health Survey revealed that deficient/marginal vitamin B12 status is a serious concern in Guatemala. Our findings from the analysis of red blood cell folate samples from Guatemalan children are consistent with our earlier findings for serum folate. This is important new information because compared to serum folate, red blood cell folate is an indicator of long-term folate status, thus suggesting that the results we obtained for the serum folate samples were not due to exposure to higher folate intakes just prior to obtaining the samples for this study. Because the folate content of their traditional diet is low, these data suggest that Guatemalan children are consuming adequate amounts of folate from supplemental sources or from fortified foods imported from other countries. Our data from children will be compared to the folate status of their mothers, the analyses of which are being completed by the CDC. Compilation of data from our research team and that of the CDC will provide the framework for a combined report on the folate status of Guatemalan children and women of reproductive age. The report will be used by the Ministry of Health to make policy decisions regarding intervention programs. Plans for manuscript preparation in conjunction with investigators at the CDC and collaborators in the Ministry of Health in Guatemala are in progress. Similar to our findings in Guatemala, the vitamin B12 status of Belizean children, as well as that of women of reproductive potential, is a serious concern, thus suggesting the need for intervention. It will be interesting to compare the folate status of Belizean children and women to that of Guatemalan children and women after we complete those analyses.
Publications
- Crider KS, Rosenthal J, Maneval DR, Kauwell GPA, Bailey LB. Effect of folic acid supplementation on DNA methylation among reproductive age women in Honduras. Electronic conference proceedings (abstract), 12th International Congress of Human Genetics Program/61st Annual Meeting of the American Society of Human Genetics, Montreal, Canada, October, 2011.
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Progress 10/01/09 to 09/30/10
Outputs
OUTPUTS: Our research team wrote a proposal/contract for the assessment of folate and vitamin B12 status in the Guatemalan children. We were awarded funding by the Centers for Disease Control and Prevention (CDC), the Guatemalan Ministry of Health, and the Institute of Nutrition for Central America and Panama (FANCAP) for the plasma folate analysis component of this study. This study, which focuses on folate and vitamin B12 status assessment in Guatemalan children, was approved by the UF IRB. Lab personnel were hired and trained, new robotic equipment was set-up and a training session for UF lab personnel was conducted at the Nutritional Biomarkers Branch, Division of Laboratory Sciences of the CDC to ensure that the procedures used to analyze the samples in our lab were identical to those used by the CDC. Frozen plasma samples were shipped from Guatemala, inventoried on receipt, and stored at -80 degrees C. Quality control and sample analyses were conducted using our Janus robotic liquid handling system coupled with microtiter plate reader and GEN 5 Data Analysis software. Data were imported into a spreadsheet and routinely evaluated to identify sample results that did not meet specified criteria. A new project proposal/contract was written and funding was received for analysis of red blood cell folate and plasma vitamin B12 in Guatemalan women of reproductive age and children. The samples have been received, and plans are being made for analysis. A third research proposal/contract was written for a new study, the Belize National Survey on Micronutrients Biomarkers among Women of Reproductive Age and Children. This study will assess the magnitude of folate and vitamin B12 deficiency in Belize as a basis for micronutrient intervention programs. Funding was approved and planning for the study was initiated with the CDC, the Belize Ministry of Health, and FANCAP. Plans were made for members of our research team to travel to Belize in early 2011 to demonstrate state-of-the-art techniques for blood collection, processing, and handling under field conditions. Our emerging partnership with Program for Appropriate Technology in Health (PATH) was continued by initiating an effort to obtain NIH funding for the development of a multiplex method to measure blood folate in tandem with other nutrient biomarkers. A draft of a proposal for submission to NIH was developed and discussed, with a plan for submission in 2011. Analysis of folate biomarkers in samples collected in Honduras was completed and submitted to co-investigators at the CDC. Dissemination: Plasma folate data from the Guatemalan study were submitted to the CDC and FANCAP in Guatemala. Plans were made to prepare a manuscript for a peer-reviewed journal and a technical report for government officials in Guatemala and funding agencies. Research planning documents related to the Belize folate/vitamin B12 status assessment project were developed and disseminated to co-investigators. A document was written by our research group describing our proposed role in the project with PATH. Upon completion of the sample analysis for the Honduran study, plans were made for the preparation of a research publication. PARTICIPANTS: Dr. Gail P. A. Kauwell, Co-PI Guatemalan studies, directed the development and adaptation of the folate analytical methodology; hired and trained lab staff to conduct folate analysis; oversaw daily operation of samples analysis; supervised the collection, organization and analysis of data; participated in conference calls to report progress and to make plans for future studies; co-wrote proposals/contracts for new funding; co-wrote new IRB protocols and completed renewal paperwork for continuation of approved projects; wrote final report including description of analytical work and presentation of data for all collaborators. Dr. Kauwell collaborated on all aspects of other projects described above. Dr. Lynn B. Bailey, Co-PI Guatemalan study: communicated with Dr. Kauwell regarding sample analysis; reviewed data; provided input on decisions regarding samples to be reanalyzed; served as the lead contact with collaborators at CDC and Central American countries; co-wrote the proposals/contracts for funding; communicated with funding agencies regarding potential new funding; communicated with collaborators regarding plans for dissemination of research data including peer-reviewed publication; served as a liaison between research staff working under her supervision and research staff working under Dr. Kauwell's supervision; oversaw budgetary issues to ensure sufficient funding for the project. David R. Maneval, Research Coordinator: support scientist for all aspects of the research program described above. Nicte Ramirez, Foundation of the Institute of Nutrition for Central America and Panama (FANCAP): Guatemalan collaborator with whom the contracts were negotiated and to whom the data were submitted. She communicated with our research team about funding, execution of contracts, shipment of samples, and data evaluation. Natalia Largaespada Beer, Belize Ministry of Health Collaborator: primary contact in Belize for the initiation of the study. Carmen Sanchez, CDC Collaborator in Belize: provided feedback on blood drawing/processing procedures; scheduled workshop at which members of our research team will demonstrate techniques for processing samples to be shipped to our lab. Dr. Jorge Rosenthal, CDC/CCHP/NCBDDD: served as a collaborator for research being conducted in Honduras, Guatemala, and Belize; worked as a liaison with our research team and collaborators with the ministries of health and funding agencies in the respective countries; participated in conference calls with our research team and other collaborators at CDC and in Central America. Dr. Krista Crider, CDC/CCHP/NCBDDD: served as a project consultant for the Honduras study. David Boyle, PATH research scientist: investigated potential funding and wrote a "white paper" describing the concept for a proposal to support a project for the development of a multiplex nutrient assessment method. CDC provided funding for some aspects of the research plan. FANCAP provided funding for the Guatemalan study; partnered with our research team to design and implement the study. PATH formed a collaborative partnership with us to develop and test new methods for determining folate and vitamin B12 status. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
It has been reported that many children and women of reproductive age in Guatemala and Belize suffer from anemia and other adverse health-related effects of B-vitamin deficiencies. The Ministries of Health in Central America and the Caribean region were provided funding by national and international agencies to assess baseline intake and blood concentrations of micronutrients. The purpose of the proposed population-based nutrient assessment studies is to provide the basis for nutrient intervention programs such as targeted supplementation and/or fortification of staple foods. Analysis of plasma folate concentrations in ~1000 Guatemalan children participating in the Guatemala National Maternal and Child Health Survey was completed by our team. The results from this study will be evaluated in consultation with the CDC, the Guatemalan Ministry of Health, and FANCAP to make recommendations for policy initiatives related to the folate status of children. The data indicate that the children's plasma folate concentrations are higher than anticipated and suggest that children are obtaining folate from supplemental sources since the folate content of traditional diets is low. This is important new information that suggests that targeted intervention to improve the folate status of children is not warranted at the present time. Because these data may reflect intermittent supplement use by children, the observed high blood folate values may be transitory. If transitory, fortification of the food supply with small daily doses of folic acid would be appropriate to maintain blood folate concentrations. Our data from children will be compared to the folate status of their mothers, the analyses of which are being completed by the CDC. Compilation of data from our research team and that of the CDC will provide the framework for a combined report on the folate status of Guatemalan children and women of reproductive age. The report will be used by the Ministry of Health to make policy decisions regarding intervention programs. Plans for manuscript preparation in conjunction with investigators at the CDC and collaborators in the Ministry of Health in Guatemala are in progress. Assessing red blood cell folate concentration will provide new insight into folate status of these populations because it reflects long-term status in contrast to plasma folate, which fluctuates with recent changes in intake. These data will be used in conjunction with the plasma folate data to more fully evaluate the folate status of the children. In addition to folate, vitamin B12 status will be assessed in children and adults in Guatemala and Belize. If the plasma vitamin B12 concentrations are low, plans will be made for targeted intervention or food fortification with this essential nutrient. Our team's input into the plans for the Belize National Survey on Micronutrients Biomarkers among Women of Reproductive Age and Children study will enable us to obtain the most appropriate sample type for our analyses and will likely enhance the quality of the samples collected and will facilitate our ability to assess the nutritional status of high-risk population sub-groups in Belize.
Publications
- Von Castel-Roberts, K, Whitman AR, Maneval DR, Bailey, LB, Kauwell GPA. Contribution of seafood to total vitamin B12 intake and status of young adult men and women. J Aquatic Food Product Technology 19:26-37, 2010
- Bor M-V, von Castel-Roberts K M , Kauwell, GPA, Stabler SP, Allen RH , Maneval DR , Bailey LB, and Nexo E. Daily intake of 4 to 7 micrograms of dietary vitamin B12 is associated with steady levels of vitamin B12-related biomarkers in a healthy young population, Am J Clin Nutr 91: 571-7, 2010.
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Progress 10/01/08 to 09/30/09
Outputs
OUTPUTS: Outputs: Completed data analysis and prepared a manuscript describing the results of our research investigating the relationship between the frequency of seafood consumption and vitamin B12 and status. Completed data analysis and prepared a manuscript comparing the association between dietary vitamin B12 intake and biomarkers of vitamin B12 status. Developed a proposal to determine serum/plasma folate concentrations from samples collected from: 1) women of reproductive potential in Ghana and Cote d'Ivoire to assess the magnitude of folate deficiency in these two countries; 2) and to determine folate status in children in Ghana. Developed and submitted proposals to investigate the analytical validity of new methods for determining folate and vitamin B12 status from dried blood spots. Wrote a book chapter examining recommended folate intakes, consumption and status. Preliminary discussions have occurred with regard to investigating the influence of folate-related genetic polymorphisms on folate status in samples from women participating in a randomized controlled folic acid intervention study. Dessimination: Two manuscripts were prepared for review in peer reviewed journals. Collaborated with a Danish research team on vitamin B12 status study. Partnered with PATH to develop a grant proposal for developing and testing new methods for determining folate and vitamin B12 status. Worked collaboratively with the Global Alliance for Improved Nutrition (GAIN) to develop an agreement that would allow us to collaborate on a research project being conducted in two African countries. Collaborated with the Centers for Disease Control and Prevention and a Honduran research team on a folic acid intervention study. Book chapter was published in a book published by CRC Press, Taylor & Francis Group. PARTICIPANTS: Individuals: Dr. Gail P. A. Kauwell, Co-PI, assisted with manuscript preparation and review for two manuscripts; co-developed a proposal and assisted with contract negotiations to determine serum folate concentrations from human blood samples collected in two African countries; co-developed and submitted proposals to investigate the analytical validity of a new methodological approach for determining the folate and vitamin B12 content from dried blood spots; co-authored a book chapter related to folate intake and status. Dr. Lynn B. Bailey, Co-PI, assisted with manuscript preparation and review for two manuscripts; co-developed a proposal and assisted with contract negotiations to determine serum folate concentrations from samples collected in two African countries; co-developed and submitted proposals to investigate the analytical validity of a new methodological approach for determining the folate and vitamin B12 content from dried blood spots; spear-headed preliminary plans to investigate the influence of folate-related genetic polymorphisms on folate status from samples obtained from women participating in a randomized controlled folic acid intervention study; co-authored a book chapter related to folate intake and status. David R. Maneval, Research Coordinator, assisted with the development of a proposal and to determine serum folate concentrations from human blood samples collected in two African countries; assisted with the development of proposals to investigate the analytical validity of a new methodological approach for determining the folate and vitamin B12 content from dried blood spots. Partner Organizations: Centers for Disease Control and Prevention provided funding for certain components of the research plan. National Fisheries Institute provided funding for certain components of the research plan. PATH - potential collaborator on a project designed to develop and test new methods for determining folate and vitamin B12 status. Global Alliance for Improved Nutrition (GAIN) Collaborators and Contacts: Dr. Kristina von Castel-Roberts, Department of Clinical and Health Psychology, University of Florida, co-authored one manuscript and assisted with manuscript preparation and review of a second manuscript. Dr. Mustafa Vakur Bor, Department of Clinical Biochemistry, Aarhus University Hospital, AS, Denmark: Conducted data analysis and co-authored one of two manuscripts. Dr. Ebba Nexo, Department of Clinical Biochemistry, Aarhus University Hospital, AS, Denmark, assisted with interpretation of data and manuscript preparation and review for one of two manuscripts. Dr. Sally P. Stabler, Denver and Health Sciences Center, Aurora, CO, reviewed and approved one of two final manuscripts. Dr. Robert H. Allen, Denver and Health Sciences Center, Aurora, CO, reviewed and approved one of two final manuscripts. Dr. Jorge Rosenthal, CDC/CCHP/NCBDDD , contact for research being conducted using samples obtained from a Honduran population. Dr. Krista Crider, CDC/CCHP/NCBDDD, served as a project consultant. Training or professional development N/A for these projects TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
Our research investigating the frequency of seafood consumption and vitamin B12 intake and status showed that seafood was the greatest contributor to vitamin B12 intake among nonvegetarians, and intake comparisons based on frequency of seafood consumption revealed that frequent seafood consumers had higher vitamin B12 intakes. Our findings, which have been accepted for publication in a peer-reviewed journal, suggest that modest seafood intake contributes to maintaining normal B12 status. These findings have implications for seafood industry professionals who may want to highlight the contribution of seafood to vitamin B12 intake and status, and to registered dietitians who work with clients/patients who need to improve their vitamin B12 status or who are searching for a natural, high quality source of this important nutrient. Our collaborative research project investigating the dietary vitamin B12 intake level consistent with maintenance of normal vitamin B12 status suggests that the current recommended dietary allowance (RDA) for this nutrient is inadequate, at least for the population between 18 and 50 years of age. A manuscript describing our findings is currently under review, and upon acceptance and publication, our findings are likely to be considered the next time the RDA for this nutrient is revised. Our research proposal and potential collaboration with GAIN was accepted, however, due to issues with the legal contract that could not be resolved between the parties (i.e., UF and GAIN), we lost the opportunity to execute this research project. The book chapter was published in the leading reference on folate and will serve as a reference for researchers, practitioners and students interested in folate nutrition. It is likely that we will not have an adequate sample size to investigate the influence of folate-related genetic polymorphisms on folate status in samples from women participating in a randomized controlled folic acid intervention study, but it is possible that analyzing these samples may provide some interesting descriptive data that might could be compared to the prevalence of this genotype in other population groups such as China.
Publications
- Von Castel-Roberts, K.M., Whittmann, A.R., Maneval, D.R., Bailey, L.B., Kauwell, G.P.A. (2010) Contribution of seafood to total vitamin B12 intake and status of young adult men and women. Journal of Aquatic Food Product Technology (in press)
- Bor MV, von Castel-Roberts KM, Kauwell GPA, Stabler SP, Allen RH, Maneval DR, Bailey LB, Nexo E. (2010) Daily intake fo 4 to 7 micrograms of dietary vitamin B12 is associated with steady levels of vitamin B12-related biomarkers in a healthy young population. American Journal of Clincal Nutrition (accepted for publication)
- Kauwell, G.P.A., Diaz, M.L., Bailey, L.B. 2010. Folate recommended intakes, consumption, and status, Chapter 19 In L.B. Bailey (ed), Folate in Health and Disease. CRC Press Taylor & Francis Group. Boca Raton, FL, p.467-490.
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