Reliability of results and interpretation of measures of 3-methylhistidine in muscle interstitium as marker of muscle proteolysis

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TO THE EDITOR: We were interested in the contribution by Tesch and colleagues to the evidence base concerning the events subsequent to acute immobilization in human muscle. Tesch and colleagues (14) used a microdialysis technique applied to human muscle in an attempt to measure an index of myofibrillar proteolysis 72 h after immobilization using the unilateral leg suspension technique. The authors discuss their results as though they had good evidence that the technique they used produces results that are sufficiently firm to be the basis of conjecture about mechanisms of protein balance in muscle after immobilization. We demur and propose that they are on very shaky ground. First, we wonder about the size of the effect reported. The authors claim it to be 44%, but calculation of the change shows it to be actually 29% with the SEs sufficiently large that they almost span the difference; SDs must overlap. Significance at the 5% level can only barely have been reached. Are the authors convinced that they have not ignored a type I error? The authors (14) begin their explanation of the advantages of the dialysis technique using 3-methylhistidine (3MeHis) by describing the gold standard method, i.e., the stable isotopelabeled amino acid tracer dilution method, as cumbersome and possibly unjustified in study of otherwise healthy subjects. We find this notion strange since Ferrando and colleagues (6, 12) have used the technique in many studies of how immobilization affects muscle protein turnover subsequent to disuse. We have also used the techniques in a wide variety of studies of proteolysis in healthy and infirm subjects (1, 2, 10, 11, 15) with no problems and, we would propose, producing results with a greater degree of certainty and biological appropriateness than those obtained by the 3MeHis dialysis technique.