Research Article: Sildenafil does not improve performance in 16.1 km cycle exercise time-trial in acute hypoxia

Date Published: January 17, 2019

Publisher: Public Library of Science

Author(s): Eric A. Carter, A. William Sheel, William K. Milsom, Michael S. Koehle, Raphael Faiss.


Sildenafil is a pulmonary vasodilator that has potential to mitigate the decrement in endurance performance caused by hypoxic pulmonary vasoconstriction. The purpose of this study was to determine the effects of sildenafil on pulmonary artery pressure, cardiac output, pulse oxygen saturation, and exercise performance at moderate simulated altitude. We hypothesized that sildenafil would reduce the decline in exercise performance in hypoxia by blunting the rise in pulmonary artery pressure and causing a relative increase in cardiac output and oxygen saturation. Twelve endurance trained men performed three experimental cycling trials at sea level and simulated moderate altitude of 3,000m (FIO2 = 0.147) after ingesting either a placebo or sildenafil 50 mg capsule in a double blinded fashion. Each test consisted of a warmup period, a 15-minute steady state period at 60% of peak power output, and a 16.1 km time-trial. All subjects experienced a decline in maximal exercise capacity in hypoxia that ranged from 6% to 24%. This decline was correlated with the reduction in pulse oxygen saturation in hypoxic maximal exercise. Sildenafil had no effect on pulmonary artery pressure, cardiac output, or pulse oxygen saturation measured during steady state exercise. There was no effect of sildenafil on mean power output during the time-trial. During high intensity cycle exercise in acute, moderate hypoxia pulmonary artery pressure is unaffected by sildenafil and does not appear to influence cardiovascular function or exercise performance.

Partial Text

Athletic competitions are frequently held at moderate altitude (1500–2999 metres, equivalent to a barometric pressure (PB) of 635–525 mmHg) for example: the 1968 Mexico City Olympics at 2250 meters, the 2017 Ski Mountaineering World Championships in Piancavello, Italy at 2251 meters, or the Livigno Sky Running World Cup at 3005 meters. Such an altitude, while not so high as to cause altitude-related illness, can negatively impact endurance performance for both athletes in competition and recreationally active individuals travelling to altitude. Endurance performance is impaired by the decrease in ambient partial pressure of oxygen (PO2), leading to reduced oxygen delivery to muscle tissues [1].

Twelve male competitive cyclists participated in this study. Their age, height, and body weight, [mean ± standard deviation (SD)] were 37 ± 9 years, 180 ± 4 cm, and 71.1 ± 8.1 kg. Participants’ mean V̇O2max was 68.6 ± 8.0 mL kg-1 min-1. All participants were sea-level residents who had not travelled above 2,000m (excluding commercial air travel) in the preceding six months. While this altitude threshold is higher than might be ideal and possibly considered a limitation, all participants reside at, and should be considered, acclimatized to sea-level. Participants maintained a consistent amount of endurance training (five sessions per week for more than one year) and competed regularly in endurance cycling or triathlon competitions (≥3 competitions per year). The study was approved by the Clinical Research Ethics Board at the University of British Columbia and all procedures were in accordance with the ethical standards of the 1964 Helsinki Declaration. Participants were informed of the procedures and possible risks involved in the study and informed consent was obtained.

In 11 participants (one was unable to complete the trial due to fatigue), normobaric hypoxia significantly reduced time-trial performance (normalized to mean power output per kilogram of bodyweight) in both the placebo hypoxia (PH) and sildenafil hypoxia (SH) condition compared to normoxia (main effect for FIO2: p < 0.01) (Fig 2). There was no significant difference between the PH and SH trials (p > 0.05).

The primary findings of this study were that sildenafil did not improve exercise performance during a 16.1 km cycle TT at a simulated moderate altitude of 3,000 m and resulted in no change in CO or PAP during sub-maximal exercise indicating that sildenafil is unlikely to be useful to athletes performing at these altitudes. There was a wide range in the detrimental effect of hypoxia on exercise performance in the TT and during the maximal exercise test. The range in the decrement in performance in the maximal exercise test was not correlated with PAP but instead driven primarily by variation in SPO2 in hypoxia.

This single-blind, randomized controlled trial confirmed that 50mg of sildenafil does not improve exercise performance during a 16.1 km cycling time-trial at a simulated altitude of 3, 000 m. Furthermore, exposure to hypoxia negatively affects the endurance performance of athletes differently and in a wide range, likely mediated by variation in SaO2. Sea-level fitness is unrelated to this range in performance and increasing fitness does not protect against the performance decline at moderate altitude. These findings indicate that the use of 50mg sildenafil is not ergogenic in moderate hypoxia. Currently, sildenafil is not a prohibited or monitored substance as per the World Anti-Doping Agency. Our results indicate that the policy need not be changed.




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