This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Sickle cell anemia (HbSS) is a global health problem, which, in the USA, affects mainly Americans of African descent, who are also likely to be affected by health care disparities and high clinical costs. The most characteristic symptom of this genetically inherited blood disorder is pain crisis, resulting from vaso-occlusion of blood vessels, and often requiring hospitalization. HbSS is associated with poor growth and development, a deficit of weight for height in adults and general morbidity, including poor immune status and chronic subclinical inflammation. All these symptoms are indicators of undernutrition. We hypothesize that the characteristicdeficits in growth and development result from greater energy and protein needs for individuals with the disease than for the general population, and that these requirements are not met by a diet that is adequate for healthy people. The increased energy needs arise because the shortened life span of the """"""""sickled"""""""" erythrocytes accelerates hemoglobin synthesis and hence, whole body protein turnover. The increased protein turnover is associated with an increased net loss of protein and thus increased protein requirement, with particular emphasis on amino acids essential for growth, repair, replacement and healthy antioxidant and anti-inflammatory status. Based on this hypothesis, a natural proposition is that extra energy and protein supplements to the daily diet, will satisfy the extra nutrient requirements, including essential amino acids for optimal lean tissue deposition and repair, increased antioxidant supply and reduced inflammation, eg L-arginine for nitric oxide (NO) production;thereby normalizing body weight, body composition and improving clinical condition. The approach to testing this hypothesis will be two-fold encompassing the following specific aims: 1. to develop an appropriate supplement directly addressing the malnutrition in HbSS pathology and 2. to investigate the effectiveness of the dietary supplement in undernourished HbSS children, aged 9 to 12 y, and adults 18+ y, by measuring changes (over 4 months) in resting energy expenditure, circulating reticulocyte count (an index of RBC production), body composition, circulating amino acids, markers of oxidant damage and pro- and anti-inflammatory proteins associated with NO production.
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