An improved method for measurement of
3-methylhistidine in blood samples has been used to assess efflux of
3-methylhistidine from the leg in
cancer patients experiencing
weight loss. Three control groups were studied: malnourished depleted patients without
cancer; comparatively well-nourished but acutely ill patients; and well-nourished controls, hospitalized for elective surgery, who showed no symptoms of
metabolic disease. Well-nourished controls and acutely ill patients had a statistically significant release of
3-methylhistidine [1.92 +/- 0.40 (S.E.) nmol/min/100 g leg tissue and 0.93 +/- 0.32 nmol/min/100 g, respectively], but
cancer patients and malnourished noncancer patients had insignificant efflux. When
nutritional support was provided, noncancer patients abolished their previously negative
tyrosine balance and increased the efflux of 3-
methylhistidine; however,
cancer patients as a group continued to show a negative
tyrosine balance, and the efflux of
3-methylhistidine continued to decrease further in them. The results in this study demonstrate that
weight loss in clinical
cancer is not dependent on increased skeletal muscle protein degradation, not even at an early stage of the disease. It seems likely that decreased
protein synthesis is a more important factor.