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Low-dose dihydroberberine is more bioavailable than high-dose berberine, pharmacokinetic study shows


  • Berberine supplementation supports glucose metabolism, but digestive upset is common due to high dosages.
  • Compared to high-dose berberine (500 mg), low-dose dihydroberberine (100 or 200 mg) significantly (p<.05) increases plasma berberine in healthy men.
  • Dihydroberberine offers a therapeutic alternative to berberine with better digestive comfort.


This randomized, double-blind, crossover, pilot study compared the absorption kinetics of berberine and Glucovantage® dihydroberberine. Berberine is a natural alkaloid with benefits for glycemic control but has low bioavailability and often causes digestive issues. Dihydroberberine has been developed to address these challenges.

Five healthy men, mean age 26 years, were assigned to four treatments in random order with 3-7 day washout periods:

  • 500 mg of berberine
  • 100 mg dihydroberberine (GlucoVantage®)
  • 200 mg dihydroberberine (GlucoVantage®)
  • Placebo (resistance dextrin)

The men consumed the supplements with meals and at least one cup of cold tap water. Blood samples were collected 0, 20, 40, 60, 90, and 120 minutes after ingestion and analyzed for berberine, glucose, and insulin.

Study participants reported 100% compliance to the protocol.

Results indicate the area under the curve (AUC) values for plasma berberine were significantly (p<.05) higher with either dose of dihydroberberine compared to berberine or placebo. In addition, the peak blood level of berberine (Cmax) shows a trend toward higher values after supplementation with dihydroberberine compared to berberine or placebo (see Table 1). No significant differences in glucose and insulin values were found between the groups. The authors attribute this non-effect to the short supplementation period and the healthy status of the participants.

Table 1. Plasma Berberine: Area Under the Curve (AUC) and Concentration Maximum (Cmax)


AUC (ng/mL × 120 min)

Cmax (ng/mL)

Dihydroberberine 200mg

929 ± 694

12.0 ± 10.1

Dihydroberberine 100mg

284.2 ± 115.9

3.8 ± 1.4

Berberine 500mg

42.3 ± 17.6

0.40 ± 0.17


20.2 ± 16.2

0.22 ± 0.18





These preliminary findings indicate low-dose supplementation of dihydroberberine (100 or 200 mg/dose) results in a higher blood level of berberine compared to a higher dose of berberine typically needed for glycemic control due to its poor absorption. In this way, dihydroberberine offers a therapeutic alternative to berberine that is more likely to promote digestive comfort and good patient compliance. 


Moon JM, Ratliff KM, Hagele AM, Stecker RA, Mumford PW, Kerksick CM. Absorption kinetics of berberine and dihydroberberine and their impact on glycemia: a randomized, controlled, crossover pilot trial. Nutrients. 2021;14(1):124. PMID: 35010998


Disclaimer: This information is for licensed healthcare professionals only to inform patient treatment. It is not intended for consumer use.