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.