Adult
Anticholesteremic Agents/pharmacology
Blood Pressure/drug effects
Energy Metabolism/drug effects
Exercise/*physiology
Exercise Test
Exercise Tolerance
Fatty Acids, Nonesterified/*metabolism
Gemfibrozil/*pharmacology
Heart Rate/drug effects
Humans
Hydroxymethylglutaryl CoA Reductases/pharmacology
Hypolipidemic Agents/*pharmacology
Lovastatin/*analogs & derivatives/pharmacology
Male
Oxidation-Reduction
Oxygen Consumption/drug effects
Pyrazines/*pharmacology
Random Allocation
Simvastatin
Single-Blind Method
We examined the impact of three lipid lowering drugs on fat oxidation during a 120 minute treadmill walk, at an exercise intensity of 50% maximal oxygen uptake (VO2 max). Subjects (N = 24) were healthy male volunteers with normal serum chemistry, assigned to three groups (n = 8). Group A received simvastatin 20 mg twice daily, Group B received gemfibrozil 600 mg twice daily, Group C received acipimox 600 mg twice daily. Each subject performed two 120 minute walks, once with drug, and once with placebo (4 days treatment plus a final dose on the morning of the exercise trial). Treatment order was reversed for half of each group. Compared to placebo, simvastatin treatment, had no impact on fat oxidation (40.9 +/- 8.6% vs 40.9 +/- 9.7%), or on plasma concentration of free fatty acids (FFA), glycerol or glucose. Treatment with gemfibrozil, showed lower fat oxidation (32.3 +/- 13.9% vs 39.7 +/- 7.9%), and lower plasma concentrations of FFA and glycerol, but differences did not reach significance at the 0.05 level. Acipimox treatment, produced significantly lower fat oxidation (36.9 +/- 12.8% vs 50.2 +/- 16.1%, P = 0.011), and lower plasma concentrations of FFA and glycerol (P = < 0.0001 and P = < 0.0001, respectively). Plasma glucose showed a trend toward lower values with acipimox (P = 0.088). These data demonstrate that selective lipid lowering drugs can reduce fat availability for exercise metabolism, placing increased demands on carbohydrates which may reduce exercise tolerance.We examined the impact of three lipid lowering drugs on fat oxidation during a 120 minute treadmill walk, at an exercise intensity of 50% maximal oxygen uptake (VO2 max). Subjects (N = 24) were healthy male volunteers with normal serum chemistry, assigned to three groups (n = 8). Group A received simvastatin 20 mg twice daily, Group B received gemfibrozil 600 mg twice daily, Group C received acipimox 600 mg twice daily. Each subject performed two 120 minute walks, once with drug, and once with placebo (4 days treatment plus a final dose on the morning of the exercise trial). Treatment order was reversed for half of each group. Compared to placebo, simvastatin treatment, had no impact on fat oxidation (40.9 +/- 8.6% vs 40.9 +/- 9.7%), or on plasma concentration of free fatty acids (FFA), glycerol or glucose. Treatment with gemfibrozil, showed lower fat oxidation (32.3 +/- 13.9% vs 39.7 +/- 7.9%), and lower plasma concentrations of FFA and glycerol, but differences did not reach significance at the 0.05 level. Acipimox treatment, produced significantly lower fat oxidation (36.9 +/- 12.8% vs 50.2 +/- 16.1%, P = 0.011), and lower plasma concentrations of FFA and glycerol (P = < 0.0001 and P = < 0.0001, respectively). Plasma glucose showed a trend toward lower values with acipimox (P = 0.088). These data demonstrate that selective lipid lowering drugs can reduce fat availability for exercise metabolism, placing increased demands on carbohydrates which may reduce exercise tolerance.