The continuous administration of physiological doses of the
branched-chain amino acids leucine,
isoleucine, and
valine (Leu-
Ile-Val) to
Yoshida sarcoma-bearing rats caused a significant increase in the survival time by 32% and a significant reduction of
tumor size after 3 weeks of growth by 33%. The shift of the
nitrogen balance to negative values during the cachectic stage was delayed but not prevented. On the average, less
nitrogen (-47 mg/day) were lost by Leu-
Ile-Val treated rats compared with untreated
tumor-bearing animals (-91 mg N/day). It appeared that Leu-
Ile-Val increased the synthesis of carcass
proteins, while it left the proteolysis rate unchanged, since the excretion of
urea and
creatinine was unaffected by these
amino acids. The daily excretion of
alpha-ketoglutarate, which is correlated with
tumor size during the early stage of growth, was decreased during the first 2 weeks by Leu-
Ile-Val, but remained for a longer period on a high level than in untreated
tumor bearers. The results point to an improvement of the metabolic resistance against carcass
protein depletion of the
tumor-bearing host by the administration of
branched-chain amino acids.