Berberine DHB

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Amount Per Serving

%Daily Value

DihydroberberineS1

200 mg

**

** Daily Value not established.

S1. GlucoVantage® is a registered
trademark of NNB Nutrition.

Microcrystalline cellulose, capsule (hypromellose and
water), ascorbyl palmitate, and silica.

Take one capsule once or twice daily, or use as
directed by your healthcare professional.
Consult your healthcare professional before use.
Individuals taking medication should discuss
potential interactions with their healthcare
professional. Do not use if tamper seal is damaged.

Berberine is a plant alkaloid derived from several different plant species customarily used in Ayurveda and traditional Chinese
medicine for various therapeutic applications. Modern clinical use and published in vivo, in vitro, and animal research studies
demonstrate that the berberine metabolite dihydroberberine (DHB) is more bioavailable than berberine and offers enhanced support
for healthy blood glucose metabolism.*1-5
Although the mechanisms underlying the beneficial effects of berberine are not entirely clear, it is hypothesized that the modulation
of gut microbes may be one mechanism by which berberine affects blood glucose metabolism.6
Results from animal and in
vitro studies suggest that berberine moderates glucose and lipid metabolism through a multi-pathway mechanism, including the
adenosine monophosphate–activated protein kinase (AMPK), c-Jun N-terminal kinase (JNK), and peroxisome proliferator-activated
receptor (PPAR)-alpha pathways.2,7 Separate research on AMPK reports activating the AMPK pathway stimulates glucose uptake
and fat oxidation while suppressing lipogenesis and gluconeogenesis.8
Berberine is also believed to be involved in the regulation of
pancreatic beta cell function, and it has been observed to inhibit the expression of disaccharidases in the duodenum, resulting in less
glucose formation from carbohydrate digestion.*9
Increasing evidence indicates that gut microbiota are also crucial mediators that regulate berberine’s pharmacokinetic and biological
effects. Berberine induces compositional alterations in gut microbiota and regulates gut microbe–dependent metabolites, factors
that contribute to its biological effects on lipid and glucose metabolism.10,11 Additionally, gut microbiota reduce berberine to DHB, its
intestine-absorbable form, which then oxidizes back to berberine after it has been absorbed into intestinal tissues and entered the
blood.*4
Berberine absorption across the intestinal epithelia is suggested to be compromised because of its “flat” chemical configuration. Berberine
displays poor bioavailability and increased potential for GI distress at the oral doses required to improve biomarkers associated with
glucose homeostasis.3
The structure of the DHB derivative of berberine is comparably open, making it more amenable to uptake. To further
explore the absorbability of berberine and DHB, researchers investigated the mechanism of action by which AMPK is activated and if using
DHB at lower doses than berberine could potentially improve the effect on adiposity and glucose metabolism in rodents fed a high-fat diet.
Berberine had to be administered at a nearly 5-fold increased dose of 560 mg/kg/d to establish the same effects demonstrated by DHB at
100 mg/kg/d. The rodents treated with the substantially lower dose of DHB showed markedly reduced adiposity and improved glucose
tolerance. Additionally, insulin sensitivity was increased in the DHB-treated animals. These results led researchers to suggest that
the difference in effects between berberine and DHB is due to the enhanced bioavailability of DHB. The findings of this study indicate
that DHB delivers the beneficial metabolic effects of berberine in a more absorbable form and at a lower dose.*5
A small, randomized, double-blind, crossover pilot study (N = 5) investigated the absorption kinetics and compared the dosing of
berberine and DHB required to achieve peak plasma concentrations. Subjects completed a 4-dose protocol of placebo, 500 mg of
berberine, 200 mg of DHB, and 100 mg of DHB. Participants ingested the first 3 doses with breakfast, lunch, and dinner, followed
by an overnight fast, then a standardized test meal accompanied by dose 4. Blood samples were collected at regular intervals
after ingestion and analyzed for berberine, glucose, and insulin. Four doses of 100 mg and 200 mg of DHB produced significantly
greater concentrations of plasma berberine across the 2-hour measurement window than a 500-mg dose of berberine or placebo.
Results suggest that irrespective of dose, DHB achieves a greater area under the curve and peak berberine concentrations when
compared with oral ingestion of berberine.*12
Purety Family Medical Clinic’s Berberine DHB contains DHB originating from berberine sourced from Berberis aristata and naturally
extracted through an enzymatic process similar to that which occurs in the human gut. With a 5-fold relative increase in absorption
rate, supplemental DHB at much lower doses than berberine has comparable beneficial metabolic effects.*4,5,12

*These statements have not been evaluated by the Food and Drug Administration.
This product is not intended to diagnose, treat, cure, or prevent any disease.

1. Imenshahidi M, Hosseinzadeh H. Phytother Res. 2019;33(3):504-523. doi:10.1002/ptr.6252
2. Zhang Q, Xiao X, Feng K, et al. Evid Based Complement Alternat Med. 2011;2011:924851. doi:10.1155/2011/924851
3. Yin J, Xing H, Ye J. Metabolism. 2008;57(5):712-17. doi:10.1016/j.metabol.2008.01.013
4. Feng R, Shou JW, Zhao ZX, et al. Sci Rep. 2015;5:12155. doi:10.1038/srep12155
5. Turner N, Li JY, Gosby A, et al. Diabetes. 2008;57(5):1414-1418. doi:10.2337/db07-1552
6. Han J, Lin H, Huang W. Med Sci Monit. 2011;17(7):RA164-RA167. doi:10.12659/msm.881842
7. Zhou L, Yang Y, Wang X, et al. Metabolism. 2007;56(3):405-412. doi:10.1016/j.metabol.2006.10.025
8. Wang Q, Zhang M, Liang B, et al. PLoS One. 2011;6(9):e25436. doi:10.1371/journal.pone.0025436
9. Chen C, Yu Z, Li Y, et al. Am J Chin Med. 2014;42(5):1053-1070. doi:10.1142/S0192415X14500669
10. Gaba S, Saini A, Singh G, et al. Bioorg Med Chem. 2021;38:116143. doi:10.1016/j.bmc.2021.116143
11. Wolf PG, Devendran S, Doden HL, et al. BMC Microbiol. 2021;21(1):24. doi:10.1186/s12866-020-02020-1
12. Moon J, Ratliff K, Hagele A, et al. Nutrients. 2021;14(1):124. doi:10.3390/nu14010124

*These statements have not been evaluated by the Food and Drug Administration.
This product is not intended to diagnose, treat, cure, or prevent any disease.