The impact of a short course of three lipid lowering drugs on fat oxidation during exercise in healthy volunteers.
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.
Department of Medicine, University of Birmingham, UK.
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A
Head
P M
PM
Jakeman
M J
MJ
Kendall
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R
Cramb
S
S
Maxwell
D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D017079:Exercise Tolerance; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D015248:Gemfibrozil / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D011719:Pyrazines / Q000494:pharmacology*; D011897:Random Allocation; D019821:Simvastatin; D016037:Single-Blind Method
D000924:Anticholesteremic Agents; D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D011719:Pyrazines; D008148:Lovastatin; D019821:Simvastatin; D006903:Hydroxymethylglutaryl CoA Reductases; C027696:acipimox; D015248:Gemfibrozil