Berberine V.S. Dihydroberberine

The Truth of the Effectiveness of the Berberine

Berberine is an alkaloid extracted from various plants. It’s primarily used to reduce insulin resistance. [1] Berberine can activate AMPK [2] while inhibiting PTP1B [3], thus increasing insulin sensitivity. Berberine products are gaining popularity among consumers who want to support healthy blood glucose management. However, feedback from different consumers varies considerably. Based on our research of consumer feedbacks on multiple brands, almost half reported that Berberine does not work when it comes to controlling blood glucose levels. Even worse, some consumers reported adverse events, such as GI issues like constipation. [4, 5]

Figure 1: Customer Feedbacks for Berberine product

If companies are using good material and recommending the right dosage, why do their products sometimes not work?

The answer is gut microbiota. In the human intestine, there are two pathways for Berberine to get into the blood and be absorbed by human tissues and organs:

1. Pathway 1: Berberine can directly pass into the blood at an extremely slow rate. [6] Part of the berberine that passes into the plasma will return to the intestine via a carrier called P-glycoprotein and make the absorption even less efficient. [7, 8]

2. Pathway 2: Berberine absorption is assisted by gut microbiota. This gut microbiota contains a specific enzyme called nitroreductase (NTR), which can reduce berberine to dihydroberberine. Dihydroberberine is rapidly absorbed and can easily pass into the blood. Dihydroberberine is then converted back to berberine quickly in the blood where it is absorbed into the tissues. Dihydroberberine has a 5X better absorption rate compared with berberine. [9, 10]

Figure 2: Absorption Pathways for Berberine and Dihydroberberine

Thus, if a consumer has a relatively optimized gut microbiota, berberine absorption (via berberine supplementation) may not be an issue. On the other hand, if a consumer doesn’t have this optimized microbiota, berberine may not be effective — and may even be problematic.

Need a berberine product that works for everyone? GlucoVantage Dihydroberberine is the solution.

Compared with berberine, GlucoVantage shows multiple advantages:

1. GlucoVantage is 5X better absorbed than berberine.

2. GlucoVantage is suitable for all groups, even for consumers who don’t have the optimized microbiota.

3. Berberine slows gut motility and results in constipation, whereas GlucoVantage doesn’t.

4. An efficacious dose of GlucoVantage can be packed in one small capsule because of the lower dosage needed. Thus, compliance is improved compared with berberine.

References

1. J. Yin, H. Xing, J. Ye, Efficacy of berberine in patients with type 2 diabetes mellitus. Metab Clin Exp 57, 712–717 (2008).

2. Y. S. Lee et al., Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes 55, 2256–2264 (2006).

3. C. Chen, Y. Zhang, C. Huang, Berberine inhibits PTP1B activity and mimics insulin action. Biochem Biophys Res Commun 397, 543–547 (2010).

4. Y.-X. Chen et al., Berberine versus placebo for the prevention of recurrence of colorectal adenoma: a multicentre, double-blinded, randomised controlled study. Lancet Gastroenterol Hepatol 5, 267–275 (2020).

5. Y. Zhang et al., Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocrinol Metab 93, 2559–2565 (2008).

6. W. Hua et al., Determination of berberine in human plasma by liquid chromatography-electrospray ionization-mass spectrometry. J Pharm Biomed Anal 44, 931–937 (2007).

7. P.-L. Tsai, T.-H. Tsai, Hepatobiliary excretion of berberine. Drug Metab Dispos 32, 405–412 (2004).

8. G.-y. Pan, G.-J. Wang, X.-D. Liu, J. P. Fawcett, Y.-Y. Xie, The involvement of P-glycoprotein in berberine absorption. Pharmacol Toxicol 91, 193–197 (2002).

9. R. Feng et al., Transforming berberine into its intestine-absorbable form by the gut microbiota. Sci Rep 5, 12155 (2015).

10. R. Feng et al., Gut Microbiota-Regulated Pharmacokinetics of Berberine and Active Metabolites in Beagle Dogs After Oral Administration. Front Pharmacol 9, 214 (2018).