Effects of neomycin alone and in combination with cholestyramine on serum methyl sterols and conversion of acetate and mevalonate to cholesterol

Abstract

Serum free methyl sterols (cholesterol precursors) and the acetate-mevalonate test (the ¹⁴C/³H ratio in serum cholesterol after an intravenous injection of a ¹⁴C-acetate-³H-mevalonate mixture) were studied in hypercholesterolaemic patients treated with neomycin, cholestyramine or their combination so as to show whether the two tests could detect changes in cholesterol synthesis (measured with faecal steroids). During a 2-week neomycin treatment the ratio increased (+55%) proportionately with the increase in faecal steroids (+29%), the decrease in serum cholesterol (−20%) being negatively correlated with the change in serum methyl sterols. After 1 to 2 years on neomycin, faecal steroids were still high and serum cholesterol low. The ratio had fallen, however, below the initial level, the respective proportionate decrease in methyl sterols being insignificant. In cholestyramine-treated patients a marked increase in cholesterol synthesis (171% increase in faecal steroids) was reflected in a proportionate increase in the ratio (+196%) and serum methyl sterols (+134%). Inclusion of neomycin in the cholestyramine treatment increased faecal steroids (overall increase 206%) and further decreased serum cholesterol (from −25 % to −38 %) but tended to reduce the ratio and serum methyl sterols. The findings suggest that neomycin activates the pre- and post-mevalonate steps of cholesterol sysnthesis.

Key-words:

• hypercholesterolaemia
• neomycin
• cholestyramine
• serum cholesterol
• faecal steroids
• bile acids
• cholesterol synthesis
• lanosterol
• methyl sterols
• acetate
• mevalonate