Long-Term Reduction of Serum Cholesterol Levels of Patients with Atherosclerosis by Small Doses of Neomycin

Abstract

The effect and tolerance of long-term oral administration of small doses of neomycin as a serum cholesterol reducing agent has been investigated. Sixteen patients were given neomycin sulfate orally for periods varying from 12 to 40.1 months, following control periods of 2.6 to 14.6 months. After an initial daily dose of 2 g of neomycin, the daily dose was varied between 0.5 and 2 g according to response. Average total serum cholesterol concentrations decreased in each of the 16 patients by 15 to 32%; the average decrease for the group was 22%. The difference was statistically significant in each patient at the 0.1% level. Serum cholesterol concentrations were maintained at the lower plateau as long as the drug was given. In an additional patient, after administration of neomycin for 2 months there was no change in serum cholesterol concentrations and the study was discontinued. Another developed severe diarrhea, nausea, and abdominal cramps during the first week of the study, so that medication was interrupted. No other serious side effects occurred. During the first 2 weeks of medication eight of the 16 patients experienced mild diarrhea or abdominal cramps or both which subsided spontaneously during continued medication. Physical examinations were carried out, kidney and liver functions remained normal, and pathogens were not grown from stool cultures.

Effect of neomycin on exchangeable pools of cholesterol in the steady state

“…The administration of neomycin was continued, and the symptoms subsided spontaneously by the end of the 2nd wk. These findings are again comparable to previous experience with the use of this drug in this laboratory (4)(5)(6)9). No other side effects were noted, the weight of the patients remained constant within 2 lbs variation, and physical examinations and the monitoring laboratory studies remained unchanged during the ad- ministration of the drug.…”

“…The differences were statistically significant at the 0.1% level. The reduction of serum cholesterol in these patients was comparable to previous results (4)(5)(6)(7)(8)(9). In the fifth patient given placebo, there was no change in the level of serum cholesterol (Table I).…”

“…), or any combination of these. It has been reported (4)(5)(6)(7)(8)(9) that the daily oral administration of 0.5-2 g of neomycin sulfate significantly reduced the concentration of serum cholesterol in man. This reduction is accompanied by a three to fivefold increase in the fecal excretion of bile acids (7,8) and a twofold increase in the fecal excretion of neutral steroids (8) during the non-steady state, a finding which suggests the involvement of pathway (c).…”

Effects of Neomycin Alone and in Combination with Cholestyramine on Serum Cholesterol and Fecal Steroids in Hypercholesterolemic Subjects

“…The overall decrease was 38%, no side effects occurred, and the patients found combination therapy convenient. Neomycin decreased serum cholesterol in This study was (1,2). Cholestyramine is an unabsorbable ion exchanger that binds bile acids in the intestinal lumen so that cholesterol elimination into the stools as bile acids is enhanced, subsequent average reductions of serum cholesterol being in the range of 20 to 30% (3).…”

Action of neomycin on the intraluminal phase of lipid absorption

“…This has led to its use as a hypocholesterolemic agent (3). The exact mechanism underlying these actions of neomycin remains uncertain but the two most plausible explanations are a toxic effect on the intestinal mucosa (4,5) and precipitation of bile acids (6, 7) and fatty acid soaps (8) from solution.…”