Irisin and exercise training in humans - results from a randomized controlled training trial

Abstract

Background: The recent discovery of a new myokine (irisin) potentially involved in health-related training effects has gained great attention, but evidence for a training-induced increase in irisin remains preliminary. Therefore, the present study aimed to determine whether irisin concentration is increased after regular exercise training in humans.

Methods: In a randomized controlled design, two guideline conforming training interventions were studied. Inclusion criteria were age 30 to 60 years, <1 hour/week regular activity, non-smoker, and absence of major diseases. 102 participants could be included in the analysis. Subjects in the training groups exercised 3 times per week for 26 weeks. The minimum compliance was defined at 70%. Aerobic endurance training (AET) consisted of 45 minutes of walking/running at 60% heart rate reserve. Strength endurance training (SET) consisted of 8 machine-based exercises (2 sets of 15 repetitions with 100% of the 20 repetition maximum). Serum irisin concentrations in frozen serum samples were determined in a single blinded measurement immediately after the end of the training study. Physical performance provided positive control for the overall efficacy of training. Differences between groups were tested for significance using analysis of variance. For post hoc comparisons with the control group, Dunnett's test was used.

Results: Maximum performance increased significantly in the training groups compared with controls (controls: ±0.0 ± 0.7 km/h; AET: 1.1 ± 0.6 km/h, P < 0.01; SET: +0.5 ± 0.7 km/h, P = 0.01). Changes in irisin did not differ between groups (controls: 101 ± 81 ng/ml; AET: 44 ± 93 ng/ml; SET: 60 ± 92 ng/ml; in both cases: P = 0.99 (one-tailed testing), 1-β error probability = 0.7). The general upward trend was mainly accounted for by a negative association of irisin concentration with the storage duration of frozen serum samples (P < 0.01, β = -0.33). After arithmetically eliminating this confounder, the differences between groups remained non-significant.

Conclusions: A training-induced increase in circulating irisin could not be confirmed, calling into question its proposed involvement in health-related training effects. Because frozen samples are prone to irisin degradation over time, positive results from uncontrolled trials might exclusively reflect the longer storage of samples from initial tests.

Trial registration: ClinicalTrials.gov NCT01263522.

Figure 1

Trial design. CON, control group; AET: aerobic endurance training; SET: strength endurance training.

Figure 2

Association between sample storage duration and serum irisin concentration. Data points represent baseline values of all groups and final tests of control subjects.

Figure 3

Changes in physical performance over the intervention period. (A) Maximum running speed (mean ± standard deviation). P-values indicate differences from control group (post hoc Scheffé test). (B) Courses of submaximal exercise heart rate (means ± standard error). Letters (a-c) on x-axes indicate the final three steps preceding the transgression to the ramp-shaped phase of the exercise tests. Group × test × step interaction: P = 0.039.

Figure 4

Changes in serum irisin concentration over the intervention period. (A) Raw values as measured (mean ± standard deviation). (B) Values after correction for the influence of sample storage duration using the slope of the regression line for baseline values (0.184 ng/ml/day; mean ± standard deviation).