Metabolic Mayhem: A Novel Case of Severe Berberine-Associated Lactic Acidosis (BALA)

Introduction: Berberine is an organic alkaloid extract used in both traditional and modern medicine. Here we present a novel case of berberine toxicity leading to refractory metabolic acidosis requiring renal replacement therapy (RRT).


Description: A 57-year-old male with diabetes mellitus and ethanol use disorder presented to the emergency department with acute renal failure, hyperkalemia, and metabolic acidosis. He had been without insulin for approximately 24 hours due to low intake after a week of generalized illness. He presented with pH 6.87, potassium 6.3, and lactate greater than 20 (mmol/L). He decompensated into an unstable wide-complex tachyarrhythmia warranting synchronized cardioversion and amiodarone infusion followed by volume expansion and sodium bicarbonate infusion. He progressed into distribution shock due to persistent acidemia. Beta-hydroxybutyrate (BHB) was 3.3 mmol/L consistent with ketosis, yet he never exhibited hyperglycemia and was not receiving any medication that would cause euglycemic ketoacidosis. Given the refractory acidemia and history of diabetes, the differential favored metformin-associated lactic acidosis. The patient denied taking metformin and mass spectrometry was negative for metformin metabolites. The patient endorsed taking a high concentration berberine supplement to treat his diabetes which included five concentrated tablets per day. The patient was started on RRT with correction of his acidemia and resolution of circulatory shock within 12 hours.


Discussion: Berberine (5,6-dihydro-9,10-dimethoxybenzo[g]-1,3-benzodioxolo[5,6-a] quinolizinium) is an isoquinoline alkaloid isolated from Coptis and Berberis genus plants. Berberine is utilized as a natural remedy to treat diabetes. We postulate that berberine accumulation from poor renal clearance led to complex I inhibition causing an increase in AMP-ATP ratio leading to increased AMPK phosphorylation promoting increased glycolysis and lactate generation causing physiology similar to metformin toxicity. BHB can be elevated with this toxicity. The patient responded in kind to hemodialysis which is the first line treatment for severe metformin toxicity based on the Extracorporeal Treatment in Poisoning (EXTRIP) criteria. This case appears to be the first case of berberine-associated lactic acidosis (BALA).