The effects of combined treatment with beta 1-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.
OBJECTIVE
We examined the effects of different combinations of beta 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 (VO2 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 mumol l-1 (105-1041), metoprolol CR + fluvastatin 277 mumol l-1 (0-647), metoprolol CR + bezafibrate 182 mumol l-1 (0-396), atenolol + fluvastatin 211 mumol l-1 (0-511), and atenolol + bezafibrate 123 mumol 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 mumol l-1 (0-84), metoprolol CR + fluvastatin 56 mumol l-1 (2-110), metoprolol CR + bezafibrate 79 mumol l-1 (0-167), atenolol + fluvastatin 90 mumol l-1 (10-170), and atenolol + bezafibrate 100 mumol 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 beta 1-selective blockers and lipid-lowering 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.
Eagles
C J
CJ
Department of Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham, UK.
Kendall
M J
MJ
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D000641:Ammonia / Q000097:blood; D000704:Analysis of Variance; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001262:Atenolol / Q000494:pharmacology; D001629:Bezafibrate / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004734:Energy Metabolism; D015444:Exercise / Q000502:physiology* / Q000523:psychology; D005221:Fatigue / Q000523:psychology; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D000077340:Fluvastatin; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D019344:Lactic Acid / Q000097:blood; D008055:Lipids / Q000097:blood*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D014280:Triglycerides / Q000097:blood
D000319:Adrenergic beta-Antagonists; D000924:Anticholesteremic Agents; D005229:Fatty Acids, Monounsaturated; D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D007211:Indoles; D008055:Lipids; D014280:Triglycerides; D019344:Lactic Acid; D000077340:Fluvastatin; D001262:Atenolol; D000641:Ammonia; D001629:Bezafibrate