The effect of branched chain amino acids on skeletal muscle mitochondrial function in young and elderly adults

Abstract

Context: A reduction in maximal mitochondrial ATP production rate (MAPR) and mitochondrial DNA (mtDNA) abundance occurs with age in association with muscle weakness and reduced endurance in elderly people. Branched chain amino acids (BCAA) have been extensively used to improve physical performance.

Objective: The objective was to determine whether an 8-h infusion of BCAA enhances MAPR equally in healthy young and elderly adults.

Methods: Using a crossover study design, we compared the effect BCAA vs. saline infusion in 12 young (23.0 +/- 0.8 yr) and 12 elderly (70.7 +/- 1.1 yr) participants matched for sex and body mass index. Skeletal muscle MAPR and mtDNA abundance were measured in muscle biopsy samples obtained before and at the end of the 8-h infusion.

Results: In young participants, MAPR with the substrates glutamate plus malate (supplying electrons to complex I) and succinate plus rotenone (complex II) increased in response to BCAA infusion, relative to a decline in MAPR in response to the saline infusion. In contrast, MAPR was unaffected by BCAA infusion in the elderly participants. Moreover, mtDNA abundance was lower in the elderly compared with the young participants but was unaffected by the BCAA infusion. Insulin and C-peptide concentrations declined over time during the saline infusion, but these declines were prevented by the BCAA infusion.

Conclusions: BCAA increased skeletal muscle MAPR in the young participants in comparison with saline, but this effect was not seen in the elderly participants indicating, that unlike in the young, BCAA does not increase muscle mitochondrial function in the elderly.

Figure 1

Branched chain amino acid concentrations. A–C, Plasma concentrations of valine, isoleucine, and leucine, respectively, during the 8-h infusion of either BCAA or saline. Data presented as mean ± sem. Mixed-effects ANOVA revealed significant treatmenttime (P < 0.001) for all three amino acids.

Figure 2

Hormones and substrates. Panels IA and IB present the plasma insulin concentrations during the 8 h infusion of either BCAA or saline. Panels IC and ID present the plasma C-peptide concentrations during the 8-h infusion of either BCAA or saline. Panels IE and IF present the plasma glucagons concentrations during the 8-h infusion of either BCAA or saline. Panels IG and IH present the plasma glucose concentrations during the 8-h infusion of either BCAA or saline. Panels II and IJ present the plasma FFA concentrations during the 8 h infusion of either BCAA or saline. Panel IIA–IIE present the insulin, C-peptide, glucagons, glucose, and FFA area under the curve (AUC) during the 8-h infusion of either BCAA or saline, respectively. Data presented as mean ± sem. Mixed-effects ANOVA was used to test the main effects of age and treatment and their interaction.

Figure 3

MAPR. A and B, Baseline mitochondrial MAPR expressed per gram of tissue during the saline (open bars) and branched chain amino acid (filled bars) infusions by age group. C and D, Baseline mitochondrial MAPR expressed per milligram of mitochondrial protein during the saline (open bars) and branched chain amino acid (filled bars) infusions by age group. MAPR was significantly lower in the elderly participants than the young when GM (complex I) was used and a trend when SR (complex II) was used. Data presented as mean ± sem. Mixed-effects ANOVA was used to test the main effects of age and treatment and their interaction.

Figure 4

MAPR. A and B, Change in MAPR in response to saline (open bars) or BCAA (filled bars) normalized to tissue weight. C and D, Change in MAPR in response to saline (open bars) or BCAA (filled bars) normalized to mitochondrial protein. MAPR was significantly lower in the elderly participants than the young when GM (complex I) was used and a trend when SR (complex II) was used. C and D, Change in MAPR in response to saline (open bars) or BCAA (filled bars). Data presented as mean ± sem. Mixed-effects ANOVA was used to test the main effects of age and treatment and their interaction.

Figure 5

mtDNA copy number. A and B, mtDNA abundance after either an 8-h infusion of saline (open bars) or BCAA (filled bars) infusions assessed using primers and probes directed to mitochondrial-encoded genes nicotinamide adenine dinucleotide hydroxide dehydrogenase-1 (ND1, A) and 4 (ND4, B) normalized to 28 sec. Data presented as mean ± sem. Mixed-Effects ANOVA was used to test the main effects of age and treatment and their interaction.