The overall goal of this proposal is to examine whether high levels of energy expenditure contribute to weight loss in patients with amyotrophic lateral sclerosis (ALS). We will examine daily energy expenditure in ALS patients, age-and gender-matched normal subjects and neurological controls using stable isotope methodology. ALS patients frequently demonstrate weight loss, nutritional compromise, sympathetic overactivity and increased oxygen cost of physical activity. This suggests that their energy expenditure is increased relative to their energy intake and body size. In this 3 year proposal, our Major Aim is to examine whether total daily energy expenditure (TDEE) and its components (resting metabolic rate and energy expenditure related to physical activity), derived from doubly labeled water, are higher in ALS patients as compared to age- and gender-matched normal subjects, and in patients with another chronic muscle wasting motor neuron disorder, the postpolio syndrome (PPS). We hypothesize that energy expenditure in ALS patients will be elevated after normalizing data for differences in fat-free mass. Thus, increased energy expenditure relative to energy requirement will be contributory in their weight loss. The Secondary Aim of this proposal is to use the data collected to develop new models to predict energy requirements as derived from biological markers of TDEE in ALS patients, and compare them to current energy recommendations. Accurate information to define suitable levels of energy intake is required to prevent or delay the weight loss that arises in ALS patients. Current recommendations for energy requirements are based on out-dated food intake data and have not considered the influence of body composition and physical activity as important determinants of energy needs. These limitations have led to the suggestion that prescription of energy requirements should be based on the measurement of energy expenditure. We propose that energy requirements will be most accurately predicted from a marker of physical activity and fat-free mass in ALS patients. In combination, these experiments will use stable isotope methodology and indirect calorimetry to examine energy metabolism in ALS patients, age-and gender-matched normal subjects and PPS patients, and offer new guidelines to predict daily caloric needs based on measures of energy expenditure that take into account disease severity in ALS patients. PROGRESS IN REPORTING PERIOD: To date we have undertaken studies of resting metabolic rate, TDEE, body composition and questionnaires on dietary intake in 3 ALS patients. In addition, we have recorded information from a 3 day food diary and completed leisure time physical activity questionnaires. FUTURE PLANS FOR PROTOCOL: We plan to undertake studies in additional ALS patients to complete our targeted goal and to compare results with those in age- and gender-matched normal subjects.
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