Bedrest is associated with protein loss by skeletal muscle. In the short term adding supplemental BCAAs to the diet during bedrest attenuates the negative N balance. The hypotheses to be tested are: (1) The effect is mainly due to a combination of increases in the tissue free amino acids and protein accretion in sites other than muscle. (2) After bedrest, the lost muscle is replaced predominantly via an increase in muscle protein synthesis (PS). Giving supplemental BCAA's during bedrest allows an earlier increase in skeletal muscle PS after bedrest because the substrates are available from the elevated tissue free amino acids levels and the higher protein content in tissues other than the atrophied muscle. One study involving 48 subjects will be run to test these hypotheses. The subjects (25-35 yr.) will be randomized into 2 groups. Subjects will be ambulatory for the first 7 days (baseline), in bed for the next 21 days (bedrest) and then ambulatory for a 7 day (recovery). Basic Nutrition for the 35 day study will be provided as `Ensure Plus' at a rate of 1.5 *REE for the pre-bed rest and recovery phases and 1.3 *REE for the bed rest phase. The two groups are: (1) control, supplemented for the bedrest period with 30 mMol.kg-l.d-l of three non-essential amino acids glycine, serine and alanine and (2) BCAA supplemented for the bed rest period with 30 mMol.kg-1.d-1 each of leucine, isoleucine and valine. Protein kinetics (whole body with 1-13C phenylalanine) and muscle (with 15N phenylalanine) and the tissue free amino acid concentrations will be determined before bedrest, after 6 d of bedrest (early), after 19 d of bedrest (late) and 2 d after the end of bedrest (recovery). Changes in lower limb protein content with bedrest will be determined by DEXA. N balance and urinary 3 MeH excretion will be determined for the duration of the study. In addition, a small follow-up study is proposed to demonstrate that it will be feasible to confirm that the same results apply to the elderly as to young adults.
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