Most Bioavailable Form of Berberine
Berberine formulations containing CYP inhibitors or absorption enhancers are the most bioavailable forms, as they can significantly increase oral bioavailability by reducing intestinal first-pass metabolism. 1
Understanding Berberine Bioavailability Challenges
Berberine is an isoquinoline alkaloid found in several medicinal plants including Hydrastis canadensis (goldenseal), Coptis chinensis, Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), and Berberis aristata (tree turmeric). 2
The major factors limiting berberine's bioavailability include:
- Poor intestinal absorption due to low water solubility 1, 3
- Extensive intestinal first-pass metabolism by cytochrome P450 enzymes (CYPs) 1
- P-glycoprotein (P-gp)-mediated efflux transport in the intestine 1, 4
- Hepatic first-pass metabolism 1
These factors contribute to berberine's extremely low oral bioavailability of only 0.68% in rats. 4
Most Effective Formulations for Improving Bioavailability
Based on the most recent evidence, the following formulations significantly improve berberine bioavailability:
1. Formulations with CYP Inhibitors
- Formulations containing compounds that inhibit intestinal CYP enzymes show the most significant improvement in bioavailability 1
- These directly address the extensive first-pass metabolism issue that severely limits berberine absorption 1
2. Formulations with Absorption Enhancers
- D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) at 2.5% concentration can improve:
- Peak concentration (Cmax) of berberine by 2.9 times
- Area under the curve (AUC) by 1.9 times 4
- TPGS works by inhibiting P-glycoprotein activity, reducing the efflux of absorbed berberine back into the intestinal lumen 4
3. Other Promising Approaches
- Lipid-based formulations that target lymphatic transport 1, 5
- Formulations that increase dissolution rates and solubility 1
- Gastro/duodenal retentive formulations that prolong contact time with absorption sites 1
- Physicochemical modifications to increase lipophilicity 1
Clinical Implications and Considerations
When selecting a berberine supplement, consider:
- Products specifically formulated with absorption enhancers like TPGS will provide significantly better bioavailability 4
- Formulations containing compounds that inhibit CYP enzymes will be more effective 1
- Standard berberine supplements without these enhancements will likely have very poor bioavailability (less than 1%) 3, 4