Histamine mediates food intake, but not muscle adaptations, following 10 weeks of resistance training in humans

Histamine receptor antagonists, commonly used for allergies, block histamine signalling and can impair adaptations to high-intensity and endurance exercise. Because it remains unclear whether this is a universal mechanism of muscle adaptation, this study investigated histamine receptor blockade effects on resistance training adaptations. Acute study: Eight men performed three resistance training sessions with intake of either placebo, H₁-receptor antihistamine (180 mg fexofenadine) or combined H₁/H₂-receptor antihistamine (540 mg fexofenadine/40 mg famotidine). Post-exercise femoral arterial blood flow (ultrasound) was unaffected by histamine blockade. Chronic study: Eighteen men performed 10 weeks of resistance training with placebo (n = 9) or H₁-receptor antihistamine (n = 9, 180 mg fexofenadine) intake before each session. Pre- and post-intervention measures included maximal strength (1RM), muscle volume (MRI), fat mass (skinfolds), fat free mass, oral glucose tolerance (OGTT), vascular function, dietary intake (food diaries) and muscle proteome profiling. Both groups similarly increased muscle volume (+7 ± 3% and +8 ± 3%; P = 0.318) and maximal strength (+14% and +20%) and reduced diastolic blood pressure (-6 and -5 mmHg), total OGTT glucose (-24% and -10%) and insulin (-10% and -9%). Unexpectedly the blockade group gained fat mass (+0.6 ± 0.6 kg), whereas the placebo group did not (-0.3 ± 0.8 kg; P = 0.011), potentially related to increased carbohydrate intake (+29 ± 20% vs. -7 ± 19%; P = 0.005). In conclusion histamine blockade did not impair resistance training-induced adaptations, suggesting that intercellular H₁-histaminergic crosstalk is not a universal mechanism across training modalities. However antihistamine intake increased food intake and fat mass, possibly reflecting histamine's role in appetite regulation. KEY POINTS: Post-resistance exercise femoral arterial blood flow is unaffected by single H₁ or combined H₁/H₂ receptor histamine blockade. H₁histamine receptor blockade does not impair resistance training adaptations, such as increases in muscle volume and maximal strength, and decreases in blood pressure, glucose and insulin levels. Histaminergic crosstalk in the muscle microenvironment is involved in endurance and high-intensity interval training adaptations, but this may not be a universal mechanism across all training modalities. Histamine blockade leads to increased habitual carbohydrate intake and fat mass following 10 weeks of resistance training, possibly due to histamine's role in hypothalamic appetite regulation.