Berberine-induced haemolysis revisited: safety of Rhizoma coptidis and Cortex phellodendri in chronic haematological diseases.

Two commonly used berberine-containing Chinese herbs, Rhizoma coptidis (RC) and Cortex phellodendri (CP), have been banned in Singapore for the past three decades due to implication of berberine in aggravating jaundice and kernicterus in neonates with glucose-6-phosphate dehydrogenase deficiency. Here we conducted a single arm, phase I/II clinical study on Chinese herbal medicine for patients with chronic cytopenic haematological conditions and we analysed a subset of 20 patients who also had RC, CP or both in their herbal concoction. We found no organ toxicity or electrolyte imbalance in these 20 patients where RC was administered for 1055 patient-days and CP for 1252 patient-days. In three patients with thalassemia intermedia, transient elevation in serum bilirubin level was observed but this was not associated with any aggravation of anaemia or liver dysfunction. A review of the literature found conflicting evidence of varying levels either supporting or refuting the allegation of neonatal jaundice and kernicterus caused by berberine. There were, however, very few clinical reports of adverse reaction attributable to RC or CP in oral TCM concoction. We conclude that based on traditional dosage and indication, the use of RC and CP in oral concoction is safe.