Progress 10/01/08 to 09/30/09
Outputs
OUTPUTS: The main output accomplished in this project during the reporting year was the successful execution of a choline intervention trial involving pregnant (n=24) and nonpregnant (n=21) women. Specifically, women were recruited from the local community through the use of fliers. Consenting women were provided all their food and beverage for a 12 week period. At least one meal had to be consumed on-site. The diet provided 350 mg/d choline and supplemental choline chloride was used to reach target choline intakes of 450 or 900 mg/d. Blood and urine were collected at weeks 0, 3, 6, 9 and 10; placental tissue and cord blood were obtained at the time of delivery for the pregnant participants. We are now in the process of analyzing the collected biological samples for a wide range of metabolites as well as readouts of genome stability and expression. Other outputs include statistical analysis of data collected the last reporting period and manuscript publication. PARTICIPANTS: Four graduate students and one-post doctoral fellow worked on this project. All were involved in the execution of the controlled feeding study previously described. TARGET AUDIENCES: The study participants received wholesome food for free throughout the feeding trial as well as $1620 in monetary compensation. The racial distribution was as follows: 6 Latino, 3 African American, 6 Asian, 1 Native American, and 29 Caucasian women. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
The main outcome accompished in this project was the training of students in the art of conducting controlled feeding studies in human study participants. Students were involved in every aspect including recruiting, screening, feeding, blood processing, and routine lab analysis. Another outcome was the translation of previously collected data so that it can be used to scientifically inform the development of recommended dietary allowances and to guide decisions regarding the therapeutic need for choline
Publications
- Shin W, Yan J, Abratte CF, Vermeylen F, and Caudill MA (2010) Choline intakes at amounts exceeding current dietary recommendations beneficially influence markers of cellular methylation in a genetic sub-group of folate deplete men. (submitted).
- Caudill MA (2010) Pre- and Postnatal Health: Evidence of an Increased Choline Requirement. J Am Diet Assc. In Revision
- Caudill MA (2010) Folate bioavailability: Implications for establishing dietary recommendations and optimizing status. Am J Clin Nutr Suppl.In Revision.
- Caudill MA, Dellschaft N, Solis C, Hinkis S, Ivanov AA, Nash-Barboza S, Randall KE, Jackson B, Solomita GN, Vermeylen F (2009) Choline intake, plasma riboflavin and the PEMT G5465A genotype predict plasma homocysteine in folate deplete Mexican American men with the MTHFR 677TT genotype. J Nutr. 139:727-733
- Ivanov A, Nash-Barboza S, Hinkis S, Caudill MA. Genetic variants in phosphatidylethanolamine N-methyltransferase (PEMT) and methylenetetrahydrofolate dehydrogenase (MTHFD1) influence biomarkers of choline metabolism when folate intake is restricted (2009) J Amer Diet Assoc. 109:313-318.
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Progress 10/01/07 to 09/30/08
Outputs
OUTPUTS: Outputs include measurements of choline/folate status biomarkers in blood samples obtained from Mexican American men participating in a controlled feeding study; measurements of D9-enriched choline and its metabolites in blood and urine; genotyping for additional common genetic variants that may interact with MTHFR C677T to influence folate/homocysteine; measurements of related B-vitamins; development of protocols for assaying the expression of choline related genes; development of protocols for measuring uracil content of human DNA; development of menus for a new feeding study involving pregnant women and nonpregnant control women; obtaining IRB approval for research conducted in the pregnant and nonpregnant women; and recruitment and screening of study participants. Results have been disseminated by publications in peer reviewed journals, presentations at scientific meetings and publications in local newsletters. PARTICIPANTS: Nothing significant to report during this reporting period. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
Impacts include the following extensions in knowledge: 1) Choline does not appear to be able to take the place of folate as a homocysteine lowering agent. 2) Excess choline is metabolized to betaine in humans 3) Choline intakes at recommended levels prevent liver dysfunction but are not optimal for other health related endpoints. 4) The folate RDA is not adequate for Mexican American men with the MTHFR 677TT genotype 5) The MTHFR 677TT genotype interacts with riboflavin, choline and the PEMT 5465 genotype to influence choline. 6) The MTHFR 677TT genotype is associated with enhanced use of betaine as evidenced by increased enrichment of dimethylglycine in urine.
Publications
- Veenema K, Solis C, Li R, Wang W, Maletz CV, Abratte C, Caudill MA. Choline intakes at AI levels are sufficient in preventing liver dysfunction in Mexican American men but are not optimal in minimizing plasma total homocysteine increases after a methionine load. Am J Clin Nutr. 2008;88:685-92.
- Stover PJ, Caudill MA. Genetic and epigenetic contributions to human nutrition and health: managing genome-diet interactions. J Am Diet Assoc. 2008;108:1480-1487.
- Hung J, Abratte CM, Wang W, Li R, Moriarty DJ, Caudill MA. Ethnicity and folate intake influence choline status in young women consuming controlled nutrient intakes. J Am Coll Nutr. 2008;27:253-259.
- Abratte CM, Wang W, Li R, Moriarty DJ, Caudill MA. Folate intake and the MTHFR C677T genotype influence choline status in young Mexican American women. J Nutr Biochem. J Nutr Biochem. 2008;19:158-165.
- Abratte CM, Wang W, Li R, Axume J, Moriarty DJ, Caudill MA. Choline status is not a reliable indicator of moderate changes in dietary choline consumption in pre-menopausal women. J Nutr Biochem. 2009;20:62-69
- Solis C, Veenema K, Ivanov AA, Tran S, Wang W, Moriarty DJ, Maletz CV, Caudill MA. Folate intake at RDA levels is inadequate for Mexican American men with the methylenetetrahydrofolate reductase 677TT genotype. J Nutr. 2008;138:1-6.
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