Stimulation of muscle ammonia production during exercise following branched-chain amino acid supplementation in humans.

1. This study examined the effects of a large (308 mg kg-1) oral dose of branched-chain amino acids (BCAAs) on muscle amino acid and ammonia (NH3) metabolism during 90 min of dynamic knee extensor exercise (64 +/- 2% of maximum workload). 2. BCAA supplementation resulted in a 4-fold increase in the arterial BCAA level (from 373 to 1537 microM, P < 0.05) and a 1.5-fold increase in the intramuscular BCAA level (from 3.4 +/- 0.2 to 5.2 +/- 0.5 mmol (kg dry weight)-1, P < 0.05) by the onset of exercise. Over the 90 min exercise period, the exercising muscle removed a total of 7104 +/- 2572 mumol kg-1 of BCAAs. In contrast, in the control trial, there was a total release of 588 +/- 86 mumol kg-1 (P < 0.05) of BCAAs. 3. The total release of NH3 over the 90 min exercise period was 2889 +/- 317 mumol kg-1 (P < 0.05) in the control trial and 4223 +/- 552 mumol kg-1 (P < 0.05) in the BCAA trial. Similarly, the total release of alanine and glutamine was 1557 +/- 153 and 2213 +/- 270 mumol kg-1, respectively, for the control trial and 2771 +/- 178 and 3476 +/- 217 mumol kg-1, respectively, for the BCAA trial. 4. The lactate release and arterial lactate values were all consistently lower in the BCAA trial than in the control trial. The net production of lactate (intramuscular shifts + total release) was lower (P < 0.05) in the BCAA trial (49.9 +/- 11.4 mmol kg-1) than in the control trial (64.0 +/- 11.7 mmol kg-1). 5. It is concluded that: (1) the administration of BCAAs can greatly increase their concentration in plasma and subsequently their uptake by muscle during exercise, and (2) long-term exercise following BCAA administration results in significantly greater muscle NH3, alanine and glutamine production, as well as lower lactate production, than is observed during exercise without BCAA supplementation. These data strongly suggest that BCAAs are an important source of NH3 during submaximal exercise and that their contribution to NH3, alanine and glutamine production can be significantly altered by changes in BCAA availability.