Reduction of Serum Cholesterol Concentrations by Neomycin, Para-aminosalicylic Acid, and Other Antibacterial Drugs in Man

Abstract

The serum cholesterol concentrations of 56 patients were studied in 112 experimental periods following the administration of neomycin and a variety of antibacterial drugs. Additional studies on the mechanism of the serum cholesterol-lowering effect of neomycin were performed. The oral administration of neomycin for 4 to 37 weeks, in daily doses of 1.5 or 2 Gm., significantly reduced the mean serum cholesterol concentration in each of 30 patients by 14 to 29 per cent (average, 21 per cent). Serum cholesterol concentrations remained low for the duration of neomycin administration, and returned to control levels after the drug was discontinued. In 10 patients the esterified fraction of cholesterol and the concentration of phospholipids decreased in the serum in proportion to total cholesterol and the distribution of cholesterol between the alpha- and beta-lipoproteins remained unchanged during neomycin administration. Combination of oral neomycin with mandelamine, phthalylsulfathiazole, isoniazid, oxytetracycline, and tetracycline did not influence the lowering effect of neomycin on serum cholesterol levels. Serum levels of neomycin after intramuscular injections of 60 mg. in 10 subjects averaged 12 times higher concentrations than was produced by the oral administration of 2 Gm. of neomycin. The intramuscular administration of 60 mg. of neomycin daily to 10 patients for 3 weeks failed to alter serum cholesterol concentrations. This suggests that the cholesterol-lowering effect of neomycin depends upon its action in the gastrointestinal tract. The concentration of neomycin was serially determined in the bile, serum, and urine of four patients. Biliary concentrations were higher, or of the same order of magnitude, after intramuscular than after oral administration of the drug. Therefore enterohepatic circulation of neomycin is unlikely. Radioactive fat-absorption tests following the reduction of serum cholesterol by longterm oral administration of neomycin showed that the absorption of dietary fats was normal in two patients and delayed but complete in two other subjects, suggesting that the cholesterol-reducing activity of neomycin is not dependent on its effect on absorption of dietary fats. The daily oral administration for 5 to 23 weeks of 8 to 12 Gm. of para-aminosalicylic acid to 15 patients lowered serum cholesterol concentrations significantly in each experiment by 14 to 44 per cet (average: 26 per cent), whereas daily doses varying between 2 and 6 Gm. reduced cholesterol less markedly. The daily addition of 2 Gm. of oral neomycin to high doses of para-aminosalicylic acid did not result in further lowering of serum cholesterol concentration. The administration of neamine (500 mg. daily), kanamycin (1 Gm. daily) and chlortetracycline (1 or 1.5 Gm. daily) lowered serum cholesterol concentrations, although less markedly than neomycin or para-amino-salicylic acid. The oral administration of phthalylsulfathiazole, isoniazid, penicillin, dihydrostreptomycin, oxytetracycline, chloramphenicol, polymyxin, erythromycin, novobiocin, bacitracin, and viomycin failed to alter serum cholesterol concentrations. The possible role of the intestinal bacterial flora in the cholesterol-lowering effect of neomycin and other antibacterial drugs, and the general relationship of intestinal bacteria to cholesterol metabolism, were discussed.