1a. Objectives (from AD-416):
1. Develop and validate mathematical models for carbon kinetics that simulate energy intake, energy regulation, and their relationship to body composition and fat stores. 2. Develop and validate practical field tools for the assessment and management of sarcopenia, dehydration, zinc status and frailty in institutionalized and community living elderly.
1b. Approach (from AD-416):
Simple monitoring of isotope clearance in breath CO2 can provide quantitative information on average energy intake. Our approach includes the use of a single stable isotope administration (C-13 palmitic acid) and monitoring its disappearance in breath CO2. We will use both mathematical modeling and clinical validation of this approach. The development and validation of new portable body composition tools will include the comparison of a hand-held caliper X-ray absorptiometer against tissue analysis by computerized tomography and the full evaluation of a nondestructive method for rapid analysis of extracellular water by X ray fluorescence analysis for stable bromine. For free-living elderly, we expect that portable body composition tools will provide an additional way to help monitor their medical, functional, and nutritional status so that they can extend safely their independent living.
3. Progress Report:
1. The response experiment for the measurement of energy intake using the kinetics of Carbon-13 (C-13) labeled palmitic acid was completed in the Metabolic Research Unit at an ARS funded research facility at Tufts University in Boston, MA. Volunteers were fed a constant-energy diet for one week for weight maintenance and then placed on a reduced (by 25%) energy intake diet for the second week of their participation. Data analysis and application of a mathematical model confirmed the “system response” hypothesis that reduced caloric intake reduces the rate of C-13 disappearance from carbon dioxide (CO2) in breath. An important parameter derived from the data was the presence of at least two active and interacting compartments in the human body for the storage and utilization of fuel: a fast pool corresponding to the liver and circulating free fatty acids, and a slow pool corresponding to the adipose tissue. Based on those results and the technical findings on the practical administration of the isotope, self-collection of breath samples, and in-house simplified mass spectrometry analysis for C-13/C-12 ratio, researchers designed a second experiment (currently in progress in the Metabolic Research Unit with 14 volunteers) to test the linearity and validity of the model. The mathematical model was modified to more accurately accommodate the experimental findings and especially the participation of body composition on the long-term kinetics of the labeled fuel. 2. ARS funded researchers from Tufts University in Boston, MA redesigned and remanufactured prototypes of a modified handheld dual-energy X-ray absorptiometry (DEXA) caliper that can be better positioned for spot body composition measurements around the thigh and upper arm. A new, more stable X-ray detector was used, and the device’s electronic circuit was redesigned to accommodate the new detector and microprocessor. This replaced the counter-based prototype with a system capable of delivering live percent fat measurements. A transmitter was also added for data downloading to nearby devices (computers or cell phones). Software was developed for the improved prototype and a manufacturer was hired to produce the microcircuits. Electronic and software testing of the new system has been completed and the instrument is ready to be licensed by the Institutional Review Board for patient use and validation against other methods. 3. A series of tests were completed using the original X-ray fluorescence (XRF) prototype instrument. Additional software was developed for the automated series of acquisition runs necessary to identify factors affecting the precision of the instrument. Based on the findings, ARS funded researchers from Tufts University in Boston, MA modified mechanical parts of the device to improve reproducibility of the positioning of each specimen. A code was developed for improving the accuracy of low-volume samples. A second version of this instrument was designed and manufactured for the analysis of evaporated plasma or other specimens in solid form. Special attention was given to the selection of materials to minimize interferences. The second instrument improved the sensitivity of bromine analysis but added to the complexity of sample preparation because of the required evaporative process. Researchers concluded that when at least 0.5 cc of plasma is available, XRF analysis in its original undisturbed liquid form is advantageous. In this case XRF analysis is performed by X-ray irradiation through the walls of the vial containing the plasma sample, eliminating the need to open the vial. This “nondestructive” analytical process fully preserves the original sample for subsequent analyses.
1. 01 A Method to Measure Energy Intake Based on Stable Isotopes and Breath Samples Energy intake evaluation is important for the management of obesity. Today, the only available tools for this purpose are based on self-reported food questionnaires which are known to be biased and difficult to apply. ARS-funded researchers at Tufts University at Boston, Massachusetts developed an alternative method to measure energy intake, one that is simple enough for field use. After the oral administration of a small amount of fatty acid labeled with a stable carbon isotope (C-13), the appearance of this isotope in breath CO2 is monitored for several days. The rate of clearance depends on the amount of food consumed. Scientists completed a controlled clinical study where volunteers were put on two different diets: one week in weight maintenance and one week in reduced caloric intake. Researchers now have the first clinical evidence of the responsiveness of this model. The results have been accepted for presentation at the Obesity 2012 meeting in September