Project Number: 6250-51000-051-10
Project Type: Specific Cooperative Agreement

Start Date: Apr 01, 2009
End Date: Mar 31, 2014

Objective:
Objective 1: Determine the absorption of dietary calcium, magnesium, iron and zinc in children and the influence of other nutrients and dietary factors on the absorption. Sub-objective 1.A: Evaluate the effects of supplemental vitamin D in enhancing calcium absorption in healthy children 4 to 8 yrs of age. Sub-objective 1.B: Assess the absorption of magnesium and zinc in healthy children 4 to 8 yrs of age. Sub-objective 1.C: Determine the effects of a diet lacking in meat (lacto-ovo vegetarian diet) on iron status in small children using a highly precise stable isotope method to measure iron status as determined by absorption of iron (reference dose). Objective 2: n/a Objective 3: Characterize dynamic indices of bone formation by quantitative histomorphometry and micro computed tomography in 7 mouse models developed in our laboratory. Objective 4: Quantitate specific gene expression by qRT-PCR in calvarial osteoblasts derived from appropriate models to clarify the specific roles of each knockout gene. Objective 5: Determine the effects of castration, iron loading, ASC feeding and plant derived antioxidants on bone parameters in vivo.

Approach:
The goal of our research is to provide data to enhance the development of nutritional guidelines, especially as related to mineral nutrition, in children. Using both human experimentation and cell culture models, we are studying methods of delivering the key minerals of calcium, zinc, and iron in the diet so as to optimize health outcomes. This is done by evaluating enhancers of mineral absorption, such as ascorbic acid, prebiotic fibers, and vitamin D and by considering nutrient:nutrient interactions that may limit mineral absorption such as an excess in the zinc:copper intake ratio. We will conduct a controlled trial of vitamin D supplementation to assess the effects of vitamin D status on calcium absorption in small children. We will evaluate different types of whole diets (lacto-ovo vegetarian) on iron status and the effects of differing intakes of zinc on zinc and copper absorption. We will determine if benefits previously seen for prebiotic fibers in enhancing calcium absorption also occur for iron absorption. These studies will utilize stable isotope techniques so as to provide accurate, practically applicable information that may be obtained from the study populations in a safe manner. In vitro studies will seek to identify genetic basis for mineral absorption and to develop appropriate models for evaluation of mineral absorption. Taken together, this project will provide novel information directly useful to government, industry, and the consumer related to dietary requirements. These data will have global application and provide a strong basis for evidence-based nutritional recommendations to be developed. Additional studies will explore the roles of aldose reductase and aldehyde reductase in modulating oxidative stress in cells, as well as their separate role in providing the starting substrates for the ascorbate synthesis pathway in mice. As a result we will have a better understanding of the role and importance of vitamin C in our diet.