Lactic acidosis associated with phenformin therapy. Evidence that inhibited lactate oxidation is the causative factor

Using uniformly labeled 14C L-lactate, we have studied the turnover and oxidation of lactic acid in a patient who presented with a mild lactic acidosis while on phenformin medication. As with other cases of lactic acidosis associated with phenformin therapy, this subject had impaired renal function as evidenced by serum creatinine levels of 2 mg./100 ml. and BUNs of 40 mg./100 ml. Comparison of the rate of lactate oxidation relative to the rate of lactate turnover in this subject while on and off phenformin therapy suggests that a prime factor leading to the elevated lactate levels in this situation in impaired peripheral aerobic metabolism. Although lactate oxidation was increased in the presence of phenformin, the control studies clearly demonstrate that aerobic metabolism was not keeping pace with the increased level of anaerobic carbohydrate metabolism brought on by the drug. It is concluded that it is this imbalance in lactate metabolism that is responsible for the lactic acidosis that accompanies phenformin therapy.