Hyperlacticacidemia in Man: Ethanol-Phenformin Synergism

Publisher Website
Google Scholar
Abstract
The effects of ethanol, phenformin, and ethanol plus phenformin on blood lactate concentrations and lactate metabolism were studied in 20 subjects. Lactate inflow, outflow and conversion to glucose were determined with the primed infusion of L—(+) lactate-U-14C for 8 hours. Resting mean blood lactate concentrations were 0.63 mM. Ethanol, phenformin, and ethanol plus phenformin increased blood lactate concentrations by 200, 150 and 500% to 1.27, 0.94 and 2.41 mm respectively. Following a single dose of phenformin (150 mg), blood lactate concentrations increased slowly to maximum values within 120–180 minutes and then declined. During the period in which lactate concentrations increased lactate inflow exceeded outflow. In contrast, ethanol produced hyperlacticacidemia by inhibition of lactate outflow rather than by increased inflow. When subjects who were pre-treated with phenformin received ethanol, increased blood lactate concentrations were accompanied by both increased lactate inflow and decreased outflow. Both ethanol and phenformin significantly altered glucose synthesis from lactate. During control experiments, 14.2% of glucose was derived from lactate. Ethanol inhibited and phenformin stimulated glucose synthesis from lactate to 8.9 and 22.5% respectively. In the presence of ethanol and phenformin 13.6% of the glucose was derived from lactate. These studies indicate that: 1) hyperlacticacidemia produced by ethanol and phenformin is due to both increased lactate production and decreased lactate utilization, 2) ethanol and phenformin exert a synergistic effect on blood lactate concentrations and 3) the inhibitory effects of ethanol on gluconeogenesis from lactate are partially antagonized by phenformin.

This publication has 0 references indexed in Scilit: