Clinical note — Berberine absorption
Berberine is poorly absorbed, with up to 5% bioavailability. In vitro data has clearly demonstrated that berberine is a potent antibacterial; however, in vivo data has established low bioavailability. Berberine has been shown to upregulate the expression and function of the drug transporter P-glycoprotein (Pgp). Pgp belongs to the super family of ATP-binding cassette transporters that are responsible for the removal of unwanted toxins and metabolites from the cell. It appears that Pgp in normal intestinal epithelia greatly reduces the absorption of berberine in the gut. In vivo and in vitro methods have been used to determine the role of Pgp in berberine absorption by using the known Pgp inhibitor cyclosporin A. Co-administration increased berberine absorption six-fold and clearly demonstrated the role of Pgp in absorption.
Increased expression of Pgp can lead to cells displaying multi-drug resistance. As previously reported a certain flavonolignan in many Berberis spp. has the ability to inhibit the expression of multi-drug resistant efflux pumps allowing berberine and certain antibiotics to be more effective.
Goldenseal is generally regarded as safe in recommended doses. Higher doses than 0.5 g of pure berberine may cause lethargy, dizziness, dyspnoea, skin and eye irritation, gastrointestinal irritation, nausea, vomiting, diarrhea, nephritis and kidney irritation.
Because controlled studies are not available, interactions are currently speculative and based on evidence of pharmacological activity. No drug interactions have been reported; however, an extract of goldenseal has demonstrated inhibition of cytochrome P450 in vitro. Theoretically these findings suggests that any drugs metabolised using this pathway may be affected. The clinical relevance of this possible interaction is unknown.
Berberine increased the blood concentration of cyclosporin A in renal transplant patients in a RCT: 52 patients received 0.2 g of berberine orally three times daily for 3 months. The final blood concentration in the berberine/cyclosporin A group was 29.3% higher than the group given cyclosporin A only. The relevance of this to oral ingestion of goldenseal is unknown — caution advised.
Contraindications and Precautions
Goldenseal is contraindicated in kidney disease because of inadequate excretion of the alkaloids. Berberine has been found to be a potent displacer of bilirubin. A review published in 1996 stated that berberine can cause severe acute haemolysis and jaundice in babies with glucose-6-phosphate dehydrogenase deficiency. Goldenseal is therefore not recommended in pregnancy, lactation or cases of neonatal jaundice. Goldenseal is also contraindicated in hypertension (BHMA 1983) as large amounts of hydrastine have been reported to restrict peripheral blood vessels and cause hypertension. The dose required to induce this effect is unknown and the ability to reach this threshold using the whole extract is unlikely; however, until this is clarified goldenseal is best avoided in hypertension.