Isoprene is a normal constituent of human breath and may be derived from the cholesterol synthetic pathway. Acute and chronic lovastatin and a cholesterol-supplemented diet were used to determine whether a mechanistic link exists between isoprene and cholesterol biosynthesis in vivo in humans. The acute effects of lovastatin, a competitive inhibitor of the rate-limiting step of cholesterol biosynthesis, on breath isoprene excretion was determined by administering a single 20, 40 or 80 mg dose of this drug to five healthy male subjects at 8 p.m. and measuring their breath isoprene levels every 4 h for one 24 h cycle before and after treatment. When compared to the baseline cycle, all three doses of lovastatin significantly reduced breath isoprene levels at 6 and 10 h post-drug treatment. Chronic lovastatin therapy (40 mg b.i.d. for 6 wk) reduced 6 a.m. breath isoprene levels (time of maximum baseline value) by 27 +/- 9% (SEM) and cholesterol synthesis measured in freshly isolated mononuclear leukocytes (ML) by 12 +/- 6%. A cholesterol-supplemented diet (1070 mg, total) ingested for 6 wk reduced breath isoprene excretion and ML sterol synthesis by 16 +/- 5 and 19 +/- 4%, respectively. The parallel decreases in isoprene excretion and cholesterol synthesis caused by these pharmacologic and dietary means suggest that breath isoprene is derived from the cholesterol synthesis pathway.

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Gallbladder stasis may be an important factor in the pathogenesis of cholesterol-gallstone formation in some individuals. We investigated gallbladder function in a group of nondieting, gallstone-free, healthy subjects with normal (22 +/- 1 kg/m2) and high (36 +/- 1 kg/m2) body mass indexes. Fasting gallbladder volume (28.2 +/- 4.4 ml) and residual volume after maximal emptying (8.4 +/- 2.3 ml) in high-body-mass index subjects were not significantly different from those of normal-body-mass index subjects (20.5 +/- 2.5 ml and 4.2 +/- 1.3 ml, respectively). The percentage of gallbladder emptying (71% +/- 5%) and the rate of gallbladder emptying (-1.9 +/- 0.3 x 10(-2) min-1) in high-body-mass index subjects in response to a maximal emptying stimulus was similar to the percentage of emptying (78% +/- 6%) and rate of emptying (-2.3 +/- 0.6 x 10(-2) min-1) in normal-body-mass index subjects. A liquid meal containing less than 1 gm fat, 14 gm protein and 6 gm carbohydrate resulted in both a decreased rate of gallbladder emptying and an increased residual gallbladder emptying and an increased residual gallbladder volume in both groups. The addition of 10 or 20 gm (but not 4 gm) of fat to the liquid meal restored gallbladder emptying to the maximal-stimulus level. These results demonstrate that gallbladder emptying in response to a single liquid meal stimulus is not altered in obesity and that dose-response relationships to fat are similar in obese and normal-weight individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

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