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, non-smoking individuals participated in a randomized double-blind placebo-controlled exercise training protocol with an experimental group receiving combined histamine H¹/H²-receptor antagonists (blockade) and a control group receiving placebo capsules (placebo) prior to each exercise training session. Following six weeks of endurance exercise training (21 training sessions), we determined the effect of blockade vs placebo on improvements in fitness and some of its determinants. The rate of improvement in peak power output over the period of the exercise training intervention was 1.62 (0.85, 2.39) % per week in the blockade vs 3.05 (2.27, 3.82) % per week in the placebo group (P < 0.05 placebo vs control). This was paralleled by blunted adaptations in vascular function and oxidative enzyme capacity but not by peak aerobic capacity (VO^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.