Histamine is a molecular transducer of adaptation to endurance exercise training in humans.

Histamine is an apparent molecular transducer of physical activity responses and antihistamines modify transcription of many of the genes responding to exercise. The purpose of this study was to determine the role of histamine-receptor activation in adaptations to endurance exercise training. Sixteen healthy, nonsmoking individuals participated in a randomized double-blind placebo-controlled exercise training protocol with an experimental group receiving combined histamine H(1)/H(2)-receptor antagonists (blockade) and a control group receiving placebo capsules (placebo) before each exercise training session. Following 6 wk of endurance exercise training (21 training sessions), we determined the effect of blockade versus placebo on improvements in fitness and some of its determinants. The rate of improvement in peak power output over the period of exercise training intervention was 1.62 (0.85, 2.39)% per week in the blockade versus 3.05 (2.27, 3.82)% per week in the placebo group (P < 0.05 blockade vs. placebo). This was paralleled by blunted adaptations in vascular function and oxidative enzyme capacity but not by peak aerobic capacity (V̇o(2peak)), which increased independent of blockade. Blocking histamine's actions during endurance exercise training via common over-the-counter antihistamines resulted in diminished gains in fitness, indicating that exercise-induced histamine release is important in generating many of the positive adaptations to exercise training that result in improvements in fitness.NEW & NOTEWORTHY Histamine appears to be intimately involved with skeletal muscle responses during and following exercise. Blocking histamine's actions during endurance exercise training by taking common over-the-counter antihistamines resulted in diminished gains in fitness. These results indicate that exercise-induced histamine release is important in generating many of the positive adaptations to exercise training.