15/07/2025
A high dose of golden seal has shown no clinically relevant interaction with metformin in a comprehensive clinical study.
Coadministration of golden seal root and rhizome with a subtherapeutic dose of the diabetes drug metformin (50 mg) was previously shown to decrease metformin levels in healthy adult participants by 25%. Given that both treatments might be co-prescribed in type 2 diabetes (golden seal for its berberine content), a new study investigated the pharmacokinetic golden seal-metformin interaction in adults with type 2 diabetes taking therapeutic doses of metformin (500 to 2250 mg per day). The potential consequent effects on clinical biomarkers of glucose control were also assessed, which might also be impacted by a pharmacodynamic interaction (an additive effect on lowering blood sugar).
The study used a complex protocol. During Arm 1 (baseline), 22 participants consumed their entire daily intake of metformin as a single oral dose. During Arm 2 (acute golden seal exposure), they were administered 3.3 g of a well-characterised oral golden seal product (550 mg whole root) 30 minutes prior to metformin. Each gram of the golden seal product contained 28.9 mg of berberine, 18.6mg of (−)-β-hydrastine and 0.73 mg of canadine. During Arm 3 (chronic golden seal exposure), they self-administered 1.1 g of golden seal three times a day for 28 consecutive days as well as metformin.
The aggregate pharmacokinetic data indicated no clinically meaningful interaction, as determined by the metformin area under the plasma concentration-time curve (AUC). However, the metformin AUC decreased by about 20%, 14% and 0% after golden seal coadministration at low (500-750 mg), moderate (1000-1500 mg), and high (2000-2550 mg) metformin doses, respectively; renal clearance and half-life remained unchanged throughout. The exploratory pharmacodynamic endpoint, HbA1c, decreased on average from 6.8% to 6.5%, regardless of the effects of golden seal on metformin pharmacokinetics.
The authors suggested that caution may be warranted for patients taking metformin concomitantly with golden seal, regardless of the unlikelihood of changes in metformin systemic exposure, due to potential additive blood glucose lowering effects.
The dose of golden seal used in this study was very high, I rarely dose more than 1.5 g per day. Yet no significant interaction was seen for more than double this dose. Also, the berberine content of golden seal is unlikely to significantly affect blood sugar, so the authors’ concern in this regard is quite conservative. It would be interesting to know if high doses of berberine, in excess of 600 mg per day, interact pharmacokinetically with metformin.
For more information see: https://pubmed.ncbi.nlm.nih.gov/39943692/