Objective: Headache, nausea, and sleeplessness at altitude [acute mountain sickness (AMS)] are major health problems for several million mountain recreationists who ascend to high altitudes each year. We aimed to test the efficacy of low-dose, slow-release theophylline for the prevention of AMS in a placebo-controlled, double-blind, randomized trial.
Methods: Twenty healthy male volunteers (mean age 34.7 y) were randomized (random allocation) to receive either 300 mg theophylline daily or placebo 5 days prior, during ascent, and during a stay at 4,559 m altitude. AMS symptoms were collected using the Lake Louise Score on each day during ascent and at high altitude. A 12-channel sleep recorder recorded sleep and breathing parameters during the first night at 4,559 m. Theophylline serum levels were drawn prior to the sleep study.
Results: Seventeen completed the entire study. Theophylline (n = 9) compared to placebo (n = 8) significantly reduced AMS symptoms at 4,559 m (Lake Louise Score: 1.5 +/- 0.5 vs placebo 2.3 +/- 2.37; p < 0.001), events of periodic breathing (34.3/h vs placebo 74.2/h; p < 0.05), and oxygen desaturations (62.3/h vs placebo 121.6/h; p < 0.01). No significant differences in sleep efficiency or sleep structure were present in the two groups. No adverse drug effects were reported.
Conclusions: Low-dose, slow-release theophylline reduces symptoms of AMS in association with alleviation of events of periodic breathing and oxygen desaturations.