EFFECT OF REGULATING CHOLESTEROL-BIOSYNTHESIS ON BREATH ISOPRENE EXCRETION IN MEN

Isoprene is a normal constituent of human breath and may be derived fr om the cholesterol synthetic pathway. Acute and chronic lovastatin and a cholesterol-supplemented diet were used to determine whether a mech anistic link exists between isoprene and cholesterol biosynthesis in v ivo in humans. The acute effects of lovastatin, a competitive inhibito r of the rate-limiting step of cholesterol biosynthesis, on breath iso prene excretion was determined by administering a single 20, 40 or 80 mg dose of this drug to five healthy male subjects at 8 pm. and measur ing their breath isoprene levels every 4 h for one 24 h cycle before a nd after treatment. When compared to the baseline cycle, all three dos es of lovastatin significantly reduced breath isoprene levels at 6 and 10 h post-drug treatment. Chronic lovastatin therapy (40 mg b.i.d. fo r 6 wk) reduced 6 a.m. breath isoprene levels (time of maximum baselin e value) by 27 +/- 9% (SEM) and cholesterol synthesis measured in fres hly isolated mononuclear leukocytes (ML) by 12 +/- 6%. A cholesterol-s upplemented diet (1070 mg, total) ingested for 6 wk reduced breath iso prene excretion and ML sterol synthesis by 16 +/- 5 and 19 +/- 4%, res pectively. The parallel decreases in isoprene excretion and cholestero l synthesis caused by these pharmacologic and dietary means suggest th at breath isoprene is derived from the cholesterol synthesis pathway.