Print this pageAmino Acids Stimulate Leg Muscle Protein Synthesis in Peripheral Arterial Disease
Lois A. Killewich, MD, Demidmaa Tuvdendorj, MD, Robert R. Wolfe, PhD and Glenn C. Hunter, MD
Section of Vascular Surgery, Surgery, The University of Texas Medical Branch, Galveston, TX
Objective: Older patients with peripheral arterial disease (PAD) and intermittent claudication have impaired walking ability, resulting from reduced lower extremity blood flow. Recent evidence suggests that intrinsic abnormalities in leg skeletal muscle may also contribute to walking intolerance in claudicants. In healthy elderly, leg muscle protein synthesis can be augmented by nutritional supplementation with amino acids; preliminary data suggest that this intervention increases muscle mass and walking ability. We investigated whether amino acid supplementation would improve leg muscle protein synthesis in elderly subjects with PAD, given that reduced leg blood flow might be presumed to restrict the availability of exogenous amino acids to muscle.
Methods: Two groups of subjects participated in the study: a group of 10 claudicants (mean age=64 years, mean ABI=0.58, 70% male) and a group of 8 age-matched healthy control subjects (mean ABI=1.1). Both groups underwent measurement of leg blood flow using strain gauge plethysmography (SGP), as well as measurement of post-absorptive (basal) and amino acid-stimulated (AA) protein synthesis in leg muscle. Protein synthesis was quantified from calf muscle biopsies by measurement of the fractional synthetic rate (FSR) of protein, using the incorporation of the stable isotope (L-[ring-2H5]) of the essential amino acid phenylalanine into muscle protein. Total protein was extracted from muscle samples, and gas chromatography-mass spectroscopy methodology was used to measure incorporation rates using a 3-pool model. Following measurement of basal FSR, all subjects were given an oral drink of 15g of essential amino acids, and the measurements of FSR were repeated. Data are expressed as mean±SD; statistical analysis of differences between the two groups with and without amino acid supplementation was performed using ANOVA with repeated measures.
Results: Calf blood flow was significantly reduced in the PAD subjects compared to the healthy controls (1.60±0.63 vs. 3.01±0.22 ml/min/100mg tissue, p=.020, t test). FSR in the basal state was not significantly different between the 2 groups (healthy=0.060±0.027 vs. PAD=0.093±0.027%/h, p=0.21). Significant increases (p<0.05) occurred in both groups in response to oral amino acid supplementation (healthy=0.135±0.058 vs. PAD=0.133±0.050%/h); the increases between the 2 groups were equivalent (p>0.05, ANOVA).
Conclusions: Despite reduced leg blood flow, elderly PAD patients synthesize calf muscle protein in the basal state in a similar fashion to healthy elderly. More importantly, administration of exogenous amino acids produces a significant increase in protein synthesis in these patients. These findings suggest that protein supplementation may provide a mechanism to increase muscle mass, improve walking ability, and increase functional status in PAD patients.