Source: CORNELL UNIVERSITY submitted to NRP
BIOMARKERS FOR OPTIMAL HUMAN CHOLINE AND CALCIUM REQUIREMENTS DURING PREGNANCY
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
SPECIAL GRANT
Reporting Frequency
Annual
Accession No.
0214282
Grant No.
2008-34324-19299
Cumulative Award Amt.
(N/A)
Proposal No.
2008-03549
Multistate No.
(N/A)
Project Start Date
Aug 1, 2008
Project End Date
Jul 31, 2009
Grant Year
2008
Program Code
[DJ]- Human Nutrition, NY
Recipient Organization
CORNELL UNIVERSITY
(N/A)
ITHACA,NY 14853
Performing Department
NUTRITIONAL SCIENCES
Non Technical Summary
Restructuring the wholesomeness of the food supply, and promoting healthy dietary habits and physical activity, increasingly are identified by the USDA as major public health objectives to secure longer lives and better quality of living throughout the life cycle. To achieve these goals, dietary recommendations must be increasingly grounded in an understanding of human nutrient dynamics, nutritional biochemistry and individual human genetics. A comprehensive understanding of the role of nutrients in basic biological processes in human health and disease will result in more accurate and scientifically informed nutrition and agriculture policies for public health benefit. Targeted manipulation of the food supply will benefit western societies that seek to optimize human nutrition throughout the life cycle and potentially replace mass fortification initiatives which may place some individuals at risk. The studies focus on the nutritional needs of vulnerable populations including underrepresented minority groups and pregnant adolescents. The overarching objective of this proposal is to increase our fundamental knowledge of human nutrition. These objectives support and advance the national goals of CSREES that include sustaining a: 1) healthy, well-nourished population, 2) safe, secure food and fiber system, 3) agricultural production system that is highly competitive in the global economy (including the training of future professionals and scientists). These studies can be initiated immediately because of the recent acquisition of a state-of-the-art Human Metabolic Research facility at Cornell University. Cornell University is uniquely positioned to address these research priorities because of its ongoing commitment of resources (facilities, faculty recruitments) that support a university-wide life-sciences initiative. This unique and targeted allocation of university resources and the associated academic environment are value-added to funds provided by this proposal, and together enable the development of nutritional genomics and human metabolic research facilities and permits Cornell scientists to address research questions in the emerging field of Human Nutritional Genomics that will directly impact food and nutrition policy.
Animal Health Component
70%
Research Effort Categories
Basic
30%
Applied
70%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
7026099101070%
8026099101030%
Knowledge Area
702 - Requirements and Function of Nutrients and Other Food Components; 802 - Human Development and Family Well-Being;

Subject Of Investigation
6099 - People and communities, general/other;

Field Of Science
1010 - Nutrition and metabolism;
Goals / Objectives
Restructuring the wholesomeness of the food supply, and promoting healthy dietary habits and physical activity, increasingly are identified by the USDA as major public health objectives to secure longer lives and better quality of living throughout the life cycle. To achieve these goals, dietary recommendations must be increasingly grounded in an understanding of human nutrient dynamics and thereby result in more accurate and scientifically informed nutrition and agriculture policies for public health benefit. The goals of this project are to initiate new human metabolic studies that address the role of calcium and choline nutrition in human health. The proposed studies use of state-of-the-art stable isotope approaches to understand human nutrient dynamics at the whole body and cellular level in healthy humans. The research outlined in this proposal will: 1) test the hypothesis that choline consumption at intakes higher than the recommended amounts will improve maternal and fetal biomarkers of choline status; 2) test the hypothesis that pregnancy alters biomarkers of choline status; 3) investigate the relationship between prenatal maternal choline intake and infant cognitive function in study participants consuming controlled choline intakes of 450 or 900 mg/d; 4) address the relationship between maternal Ca intake and vitamin D status on maternal bone loss and fetal bone growth during pregnancy; and 5) assess the impact of maternal Ca intake and vitamin D status during pregnancy on bone mineral content and relationships between maternal and neonatal calcitropic status at parturition. The experiments will be conducted at the Cornell Human Metabolic Research Facility (HMRU) at Cornell University. Results from these human metabolic studies are anticipated to support the determination of dietary recommendations. These objectives support and advance the national goals of CSREES that include sustaining a: 1) healthy, well-nourished population, 2) safe, secure food and fiber system, 3) agricultural production system that is highly competitive in the global economy, including the training of future professionals and scientists.
Project Methods
The first project will test the 3 hypotheses. First, it is proposed that choline consumption at intakes higher than the recommended amounts will improve maternal and fetal biomarkers of choline status. This hypothesis will be tested by measuring biomarkers of choline status in blood obtained from pregnant women consuming controlled intakes of 450 or 900 mg/d throughout the third trimester of pregnancy and in cord blood obtained from the newborn at delivery. This aim will take 18-24 months to accomplish. Second, it is proposed that pregnancy alters biomarkers of choline status. This hypothesis will be tested by comparing biomarkers of choline status in pregnant women versus those measured in nonpregnant women under conditions of equivalent levels of choline intake (i.e., 450 or 900 mg/d choline). This aim will take 18-24 months to accomplish. Third, the project proposes to provide novel preliminary data on the relationship between prenatal maternal choline intake and infant cognitive function in study participants consuming controlled choline intakes of 450 or 900 mg/d. Specifically, cognitive tests that target functions modulated by basal forebrain cholinergic neurons and their projection systems (i.e., frontal cortex and hippocampus) will be performed on the infant at months 3, 9 and 12. Studies of prenatal choline supplementation in rodents have demonstrated effects on these specific functions. This aim will take up to 30 months to accomplish. The second project will assess the impact of maternal calcium intake and vitamin D status during pregnancy on longitudinal changes in maternal bone mass and fetal bone growth and maternal and fetal calcitropic hormone status. The first specific aim will address the relationship between maternal Ca intake and vitamin D status on maternal bone loss and fetal bone growth during pregnancy. The second specific aim will assess the impact of maternal Ca intake and vitamin D status during pregnancy on bone mineral content and relationships between maternal and neonatal calcitropic status at parturition. This proposal is supported by core facilities that integrate nutritional biochemistry, genomics and human nutrition with murine and human genetics to study problems of human nutrition. The proposed studies will further strengthen research capacity using the resources available in the newly updated Human Metabolic Research Facility (HMRU). The experiments outlined in this proposal are focused primarily on the use of state-of-the-art stable isotope approaches to understand human nutrient dynamics at the whole body and cellular level in healthy humans. The research projects outlined below will further expand the Cornell unique strength in Nutrition: translating information obtained from basic human metabolic research into recommendations that are grounded in an understanding of human nutrient dynamics and thereby better inform policy for public health benefit.

Progress 08/01/08 to 07/31/09

Outputs
OUTPUTS: The goals of this project are to initiate human metabolic studies that address the role of calcium and choline nutrition in human health. Calcium Homeostasis During Pregnancy: The objective of this component of the project was to assess markers of calcium homeostasis during pregnancy in relation to measures of bone homeostasis in the mother / neonate dyad. Samples for this study were obtained from our study of maternal and fetal bone health in pregnant adolescents (Teen Bone Study). Recruitment for the Teen Bone Study began in Rochester, NY in December, 2006. As of May 2009, a total recruitment of 164 girls have been recruited. All of the osteocalcin measures have been completed for teens that have completed the study to date. Serum osteocalcin was significantly higher in cord verses maternal circulation at delivery, by 8.9 +/- 8.0 ng/mL on average. Osteocalcin increased significantly during gestation such that final concentration in maternal blood at delivery was 1.87 +/- 2.76 ng/mL higher than that observed at mid-gestation. Maternal mid-gestation levels of osteocalcin were positively correlated with values at delivery (p < 0.0001, n = 67), and with neonatal levels at birth (p = 0.0119, n = 59). Vitamin D status in this group of teens was suboptimal as 51% of teens were vitamin D insufficient (25(OH)D ≤ 20 ng/mL) at mid-gestation, and 51% of neonates also had insufficient 25(OH)D levels at birth. Intact PTH significantly increased from mid-gestation to delivery in teens (p = 0.0003, n = 21), and 46% had elevated PTH (PTH > 46 pg/mL) at delivery. The elevations in parathyroid hormone observed during pregnancy are unexpected and have previously only been reported in international settings where calcium intakes are markedly lower. Levels of a serum marker of bone resorption (N-telopeptide; NTX) and serum levels of a marker of bone formation (osteocalcin; OC) were also positively correlated in maternal blood at mid-gestation (p = 0.002, n=86), and at delivery (p = 0.0151, n=75), and in neonatal circulation at delivery (p = 0.0323, n=62). Additional analyses are ongoing. Optimal Human Choline Requirements During Pregnancy: To date, 52 nonpregnant and 26 pregnant women have contacted us about possible participation. Of these, 20 nonpregnant and 10 pregnant women have been screened for the study with start dates beginning as early as January 12 2009. Recruitment and screening is on-going and will continue until target numbers are met. A choline stock solution has been prepared, measured and is stored at 4C. For consumption during the next 3 months, appropriate volumes of the choline stock solution have been dispensed into 50 mL conical tubes (n=700), filled with crangrape juice and stored at -20C until ready for use. In addition, prenatal vitamin supplements and D9-choline have been purchased. Protocols for all meals have been developed and tested. Graduate students have been trained (n=4) along with several undergraduate research assistants (n=4). The feeding phase began January 12 2009 with 2-3 students working each shift (breakfast, lunch and dinner). PARTICIPANTS: Not relevant to this project. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Not relevant to this project.

Impacts
These objectives support and advance the national goals of CSREES that include sustaining a: 1) healthy, well-nourished population, 2) safe, secure food and fiber system, 3) agricultural production system that is highly competitive in the global economy, including the training of future professionals and scientists. Results obtained to date have highlighted the vulnerability of pregnant teens with respect to bone health based on observed losses of maternal bone across pregnancy and based on findings that show maternal diet is significantly related to fetal bone growth. In many instances the observed biochemical changes during pregnancy in this age group differ from those previously reported among pregnant adult US women. These data are novel and will add to the existing literature to promote maternal and fetal bone health among pregnant adolescents. All necessary reagents are on hand to complete the analyses of the remaining biochemical indicators in these study populations. Studies of Optimal Human Choline Requirements During Pregnancy are ongoing.

Publications

  • No publications reported this period