The effects of combined treatment with beta1-selective receptor antagonists and lipid-lowering drugs on fat metabolism and measures of fatigue during moderate intensity exercise: a placebo-controlled study in healthy subjects

Aims We examined the effects of different combinations of b 1 -selective adrenoceptor blockers and lipid-lowering drugs, on fat metabolism and fatigue during moderate intensity exercise in 14 healthy young volunteers.Methods The study was a randomized crossover design, each subject completing 5, 90 min walks at 50% of predetermined maximal oxygen uptake (VO 2 max), one following each 3 day treatment period with either: atenolol 100 mg and bezafibrate 400 mg, atenolol 100 mg and fluvastatin 40 mg, metoprolol CR 100 mg and bezafibrate 400 mg, metoprolol CR 100 mg and fluvastatin 40 mg, or placebo.Results Plasma free fatty acid (FFA) concentration during exercise was significantly reduced on all treatments, in comparison with placebo, P=0.0001.Following 90 min of exercise FFA levels were as follows: placebo 573 mmol l -1 (105-1041), metoprolol CR+fluvastatin 277 mmol l -1 (0-647), metoprolol CR+bezafibrate 182 mmol l -1 (0-396), atenolol+fluvastatin 211 mmol l -1 (0-511), and atenolol+bezafibrate 123 mmol l -1 (0-352).Total fat oxidation during exercise was also reduced on all treatments in comparison with placebo: 38.1% (2-74), compared with 29.1% (0-61) on metoprolol CR+fluvastatin, P=0.02, 26.2% (2-51) on metoprolol CR+bezafibrate, P=0.002, 25.5% (3-48) on atenolol+fluvastatin, P= 0.009, and 22.8% (0-47) on atenolol+bezafibrate treatment, P=0.0002.Plasma ammonia concentration was elevated on all treatments during exercise in comparison with placebo.After 90 min of exercise, plasma ammonia levels were as follows: placebo 37 mmol l -1 (0-84), metoprolol CR+fluvastatin 56 mmol l -1 (2-110), metoprolol CR+bezafibrate 79 mmol l -1 (0-167), atenolol+fluvastatin 90 mmol l -1 (10-170), and atenolol+bezafibrate 100 mmol l -1 26-174).In comparison with placebo, metoprolol CR+fluvastatin had the least adverse impact on measures of perceived exertion and the 'feeling scale' during exercise.Metoprolol CR+bezafibrate, atenolol+fluvastatin, and atenolol+bezafibrate treatments had greater adverse effects, particularly on perceived 'cardiorespiratory effort' and 'feeling scale' scores.Conclusions In healthy volunteers, combinations of b 1 -selective blockers and lipidlowering drugs were associated with significant reductions in fat metabolism, increased plasma ammonia levels, and raised the perception of effort during exercise, in comparison with placebo.Metoprolol CR+fluvastatin had the least effect, combinations metoprolol CR+bezafibrate and atenolol+fluvastatin had intermediate effects, and atenolol+bezafibrate had the most adverse effect.