Histamine‐Receptor Antagonists Affect Endurance Exercise Performance in Highly Competitive Cyclists
Authors: Ely Matthew R. , Sieck Dylan C. , Mangum Joshua E. , Larson Emily A. , Brito Leandro C. , Minson Christopher T. , Halliwill John R. 
Published: June 2021

Histamine‐receptor antagonists (“antihistamines”) are widely used among endurance athletes and are not currently banned by the World Anti‐Doping Agency. Our lab has recently shown that a single dose of antihistamines prior to muscle‐damaging exercise attenuates strength loss and muscle pain in the 72 hours following exercise. Histamine, produced within muscle, may be a factor in exercise‐induced muscle pain/discomfort and, therefore, perception of effort, as group III/IV muscle afferents (nociceptive neurons) are sensitized via activation of H1 and H2 receptors. Histamine may have more influence on muscle pain and effort sensations during long‐duration exercise than short‐duration, because the activity of histidine decarboxylase (the enzyme that creates histamine) increases with exercise duration. Therefore, the purpose of this experiment was to determine if combination H1/H2 antihistamines increase endurance exercise performance. It was hypothesized that H1/H2 antihistamines would decrease the time to completion of a fixed‐distance time‐trial compared to placebo, and the effect would be greater following an endurance‐exercise bout. Eleven (3F) highly competitive cyclists (Cat 1–3) performed six 10 km time‐trials on separate days. The first two trials served as a familiarization, and repeatability was assessed by calculating a coefficient of variation (CV) between times to completion. The next 4 trials were performed in a randomized‐block order. Two were preceded by 120 min of seated rest and two by 120 min of steady‐state cycling at 50% VO2peak. Within those blocks, volunteers consumed either antihistamines (540 mg fexofenadine; a H1 receptor blocker, and 300 mg of ranitidine; a H2 blocker) or placebo 60 min prior to the start of rest/exercise. The main outcome variable was 10 km time to completion. Additionally, rating of perceived exertion (RPE), isometric quadriceps muscle strength, blood glucose, and blood lactate were measured prior to and following the time‐trials. Conventional statistics (2‐Way Repeated Measures ANOVA), effect size (ES = Cohen's dz), 95% CI, and CV from familiarization trials were used to determine the presence, strength, and meaningfulness of differences, respectively, between the trials. There was a significant reduction in performance with antihistamines compared to placebo (+10.5 ± 3.8 s, mean±SEM, drug effect p=0.002), the reduced performance tended to be exacerbated by prior exercise (p=0.057) but there was no drug by prior exercise interaction (p=0.716) (Figure 1). The day‐to‐day 10 km performance variability (CV) was 0.98%. The percent change between placebo and antihistamine was likely trivial for time‐trials following rest (mean −0.87%, 95%CI −2.02 to 0.29%) (ES=0.505) and potentially harmful following exercise (mean −1.2%, 95%CI −2.45 to 0.05%) (ES=0.646). There were no drug effects on changes (pre to post time‐trial) in isometric muscle strength (p=0.607), RPE (p=0.828), blood glucose (p=0.964) or lactate (p=0.402) between antihistamine and placebo conditions. Thus, contrary to our hypothesis, blocking histamine's receptors slowed performance of 10 km time‐trials in highly competitive cyclists and did not influence perception of effort.Support or Funding InformationEugene & Clarissa Evonuk Memorial Graduate FellowshipThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.