Fresh feces from 25 patients were homogenized and incubated with labeled cholic or chenodeoxycholic acid. After 24 hours of incubation, the percent change to the 7a-dehydroxylated form was measured. In 11 patients, the oral administration of 2g of neomycin daily significantly reduced the levels of serum cholesterol (from an average of 316 mg/100 ml plasma to 237 mg/100 ml plasma) and markedly inhibited the extent of 7a-dehydroxylation of cholic acid (from 89% to 9%); in 2 patients whose serum cholesterol levels were not lowered, the degradation of cholic acid remained unchanged (control 93%, neomycin 91%). In 5 patients the administration of kanamycin reduced serum cholesterol levels (from 280 mg/100 ml plasma to 252 mg/100 ml plasma) and also inhibited 7a-dehydroxylation of cholic acid (from 92% to 21%); in 3 additional patients this drug failed to lower serum cholesterol concentrations and had no effect on bile acid degradation (control 91%, kanamycin 92%). Similar results were obtained with chloramphenicol in 3 patients, and equivocal results were obtained with chlortetracyeline in 3 patients. The correlation coefficient between undegraded cholic acid and percent decrease in serum cholesterol concentrations (r = 0.732) was statistically significant ( P < 0.001). It is proposed that serum cholesterol levels might be controlled in part by the prevalence of bile acid-degrading bacteria within the gastrointestinal tract.
The combined oral administration of neomycin (2 g daily) and clofibrate (2 g daily) reduced significantly serum cholesterol levels in 15 of 16 patients. Most of these patients had type II hypercholesterolemia and clinical evidence of arteriosclerosis. The combined regimen of the two drugs was more effective in reducing cholesterol levels in about one third of the patients than administration of either one of these drugs alone. The average decrease of serum cholesterol in these patients while on the combined regimen was 38% from the control values. Control serum triglyceride levels were normal in most patients, thus the effect of the drugs on triglycerides was moderate. No noteworthy side effects were encountered. It is felt that a trial of treatment by the combined administration of neomycin and clofibrate is justified in patients with type II hypercholesterolemia and arterioscleroisis who are resistant to other forms of treatment or to treatment by a single drug.
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