Clinical Benefits of Berberine

Berberine is a natural alkaloid compound found in various plants, particularly in the roots, rhizomes, and stems of plants belonging to the Berberis species (barberry) and other related plants like Oregon grape (Mahonia aquifolium) and goldenseal (Hydrastis canadensis). A significant body of clinical evidence highlights a multitude of benefits:


Blood Glucose Regulation - A Promising Tool in Diabetes Management:
Numerous clinical trials have investigated the effects of Berberine on blood glucose regulation, particularly in patients with type 2 diabetes. Results have consistently shown that Berberine can significantly improve fasting blood glucose levels, postprandial glucose response, and HbA1c levels.1 Its mechanism of action involves enhancing insulin sensitivity and increasing glucose uptake in cells, making it a promising adjunctive therapy for diabetes management.1,2


Lipid Profile Modulation - Aiding Cardiovascular Health:
Berberine's impact on lipid metabolism has been extensively researched, and the results are noteworthy. Clinical studies have revealed that Berberine supplementation can effectively reduce total cholesterol, LDL cholesterol, and triglyceride levels while elevating HDL cholesterol.3,4 These lipid-lowering effects are essential in managing cardiovascular risk factors and promoting heart health.


Weight Management - Supporting Sustainable Weight Loss:
In the context of obesity and weight loss, Berberine has shown promise as a weight management aid. Clinical trials have demonstrated that Berberine supplementation can lead to significant reductions in body weight, body mass index (BMI), and waist circumference.5,6 Some of the ways these benefits are realized include Berberine’s ability to activate AMP-activated protein kinase (AMPK),7 inhibit the activity of certain enzymes responsible for fat storage (PAPs),8 inhibit the differentiation and growth of fat cells (adipocytes),9 and promote the recruitment and activation of brown adipose tissue which helps burn calories and reduce weight.10


Anti-Inflammatory Properties - Potential in Various Health Conditions:
Clinical studies have shown that Berberine can inhibit NF-κB, modulate ApoM/S1P pathway, inhibit COX-2, modulate Wnt/Beta-Catenin signaling pathway, increase ZIP14 expression11 as well as repress inflammatory markers tumour necrosis factor-α, interleukin-6 and IL-1β, as well as prostaglandin E2, inducible nitric oxide synthase and cyclooxygenase-2.12 Berberine's anti-inflammatory properties have been investigated in a range of health conditions including ulcerative colitis,13 alcohol induced liver injury,14 as well as atherosclerosis and much more,15 and may offer therapeutic potential in numerous inflammatory-related disorders.


Gastrointestinal Health - Supporting Gut Microbiome:
Berberine's antimicrobial activity extends to the gastrointestinal tract, where it can help restore balance to the gut microbiome. Clinical evidence suggests that Berberine can inhibit pathogenic bacteria while promoting the growth of beneficial gut flora.16, 17 This may be particularly beneficial in managing gastrointestinal infections and supporting overall digestive health and may partly explain many of the systemic health benefits of berberine.

The clinical evidence surrounding Berberine is undoubtedly promising, supporting its potential as a valuable natural supplement with diverse therapeutic applications. Berberine has emerged as a noteworthy compound worth considering in clinical practice.

The many clinically proven benefits of Berberine are impressive. However, many people don’t realize that Berberine has also been shown to have very poor absorption.18 This is due to a combination of factors including low solubility19, limited permeability,20 and high first-pass metabolism effects20 wherein a significant portion of berberine is metabolized by the liver and quickly excreted.21 In fact, extensive clinical references indicate that more than 99% of Berberine is excreted and does not enter the bloodstream.21 In other words, less than 1% of Berberine HCl taken orally actually gets absorbed.

As a result of this poor absorption, clinical studies showing berberine’s impressive results tend to be at high doses (i.e. 900-1500mg / day).25 Unfortunately, at high doses, berberine often causes gastric distress, including abdominal pain, nausea, and vomiting, in 30-40% of patients.25 Outside of clinical trials, customers using berberine experiencing gastric distress often respond by lowering their daily dose. Unfortunately, this often results in customers taking sub-clinical doses, which limits the therapeutic benefit given the limited percentage of berberine getting absorbed (i.e. less than 1%).

Provita Berberine TPGS includes a blend of support ingredients to significantly enhance its absorption. These include tocophersolan,21 chitosan,22 and caprylic acid.23 Each of these support ingredients enhances berberine absorption on average 300% over baseline (individually). One of these ingredients was even shown to increase absorption as much as 35x or 3500% over baseline!24

The combination of these ingredients dramatically enhances absorption into the bloodstream and helps maximize therapeutic benefits of berberine HCl. However, as with any intervention, it is vital to consider individual patient characteristics, potential drug interactions, and proper dosing when incorporating Berberine into treatment plans. Further research and larger-scale clinical trials will be instrumental in uncovering the full extent of Berberine's therapeutic potential.

References:

1. Xie W, Su F, Wang G, Peng Z, Xu Y, Zhang Y, Xu N, Hou K, Hu Z, Chen Y, Chen R. Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis. Front Pharmacol. 2022 Nov 16;13:1015045. doi: 10.3389/fphar.2022.1015045.
2. Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008 May;57(5):712-7. doi: 10.1016/j.metabol.2008.01.013.
3. Ju J, Li J, Lin Q, Xu H. Efficacy and safety of berberine for dyslipidaemias: A systematic review and meta-analysis of randomized clinical trials. Phytomedicine. 2018 Nov 15;50:25-34. doi: 10.1016/j.phymed.2018.09.212. Epub 2018 Sep 28.
4. Zhao Y, Yang YY, DU YW, Yang HM, Wu SX. [Systematic review and Meta-analysis on efficacy and safety of berberine for dyslipidemia]. Zhongguo Zhong Yao Za Zhi. 2020 Feb;45(3):664-673. Chinese. doi: 10.19540/j.cnki.cjcmm.20190626.501.
5. Asbaghi O, Ghanbari N, Shekari M, Reiner Ž, Amirani E, Hallajzadeh J, Mirsafaei L, Asemi Z. The effect of berberine supplementation on obesity parameters, inflammation and liver function enzymes: A systematic review and meta- analysis of randomized controlled trials. Clin Nutr ESPEN. 2020 Aug;38:43-49. doi: 10.1016/j.clnesp.2020.04.010.
6. Xiong P, Niu L, Talaei S, Kord-Varkaneh H, Clark CCT, Găman MA, Rahmani J, Dorosti M, Mousavi SM, Zarezadeh M, Taghizade-Bilondi H, Zhang J. The effect of berberine supplementation on obesity indices: A dose- response meta- analysis and systematic review of randomized controlled trials. Complement Ther Clin Pract. 2020 May;39:101113.
7. Jin Y, Liu S, Ma Q, Xiao D, Chen L. Berberine enhances the AMPK activation and autophagy and mitigates high glucose- induced apoptosis of mouse podocytes. Eur J Pharmacol. 2017 Jan 5;794:106-114. doi: 10.1016/j.ejphar.2016.11.037. Epub 2016 Nov 22.
8. Heidarian E, Rafieian-Kopaei M, Khoshdel A, Bakhshesh M. Metabolic effects of berberine on liver phosphatidate phosphohydrolase in rats fed on high lipogenic diet: an additional mechanism for the hypolipidemic effects of berberine. Asian Pac J Trop Biomed. 2014 May;4(Suppl 1):S429-35. doi: 10.12980/APJTB.4.2014C474.
9. Hu Y, Davies GE. Berberine inhibits adipogenesis in high-fat diet-induced obesity mice. Fitoterapia. 2010 Jul;81(5):358-66. doi: 10.1016/j.fitote.2009.10.010. Epub 2009 Oct 25.
10. Wu L, Xia M, Duan Y, Zhang L, Jiang H, Hu X, Yan H, Zhang Y, Gu Y, Shi H, Li J, Gao X, Li J. Berberine promotes the recruitment and activation of brown adipose tissue in mice and humans. Cell Death Dis. 2019 Jun 13;10(6):468. doi: 10.1038/s41419-019-1706-y.
11. Izadparast F, Riahi-Zajani B, Yarmohammadi F, Hayes AW, Karimi G. Protective effect of berberine against LPS-induced injury in the intestine: a review. Cell Cycle. 2022 Nov;21(22):2365-2378. doi: 10.1080/15384101.2022.2100682. Epub 2022 Jul 19.
12. Hashemzaei M, Rezaee R. A review on pain-relieving activity of berberine. Phytother Res. 2021 Jun;35(6):2846-2853. doi: 10.1002/ptr.6984. Epub 2020 Dec 19.
13. Zhu C, Li K, Peng XX, Yao TJ, Wang ZY, Hu P, Cai D, Liu HY. Berberine a traditional Chinese drug repurposing: Its actions in inflammation-associated ulcerative colitis and cancer therapy. Front Immunol. 2022 Dec 6;13:1083788. doi: 10.3389/fimmu.2022.1083788.
14. Ke X, Zhang R, Li P, Zuo L, Wang M, Yang J, Wang J. Hydrochloride Berberine ameliorates alcohol-induced liver injury by regulating inflammation and lipid metabolism. Biochem Biophys Res Commun. 2022 Jun 25;610:49-55. doi: 10.1016/j.bbrc.2022.04.009. Epub 2022 Apr 7. Erratum in: Biochem Biophys Res Commun. 2022 Aug 20;617(Pt 1):68- 69.
15. Hou Q, He WJ, Wu YS, Hao HJ, Xie XY, Fu XB. Berberine: A Traditional Natural Product With Novel Biological Activities. Altern Ther Health Med. 2020 Jul;26(S2):20-27.
16. Zhang L, Wu X, Yang R, Chen F, Liao Y, Zhu Z, Wu Z, Sun X, Wang L. Effects of Berberine on the Gastrointestinal Microbiota. Front Cell Infect Microbiol. 2021 Feb 19;10:588517. doi: 10.3389/fcimb.2020.588517.
17. Habtemariam S. Berberine pharmacology and the gut microbiota: A hidden therapeutic link. Pharmacol Res. 2020 May;155:104722. doi: 10.1016/j.phrs.2020.104722. Epub 2020 Feb 24.
18. 18. Habtemariam S. The Quest to Enhance the Efficacy of Berberine for Type-2 Diabetes and Associated Diseases: Physicochemical Modification Approaches. Biomedicines. 2020 Apr 18;8(4):90. doi: 10.3390/biomedicines8040090.
19. Feng, R., Shou, JW., Zhao, ZX. et al. Transforming berberine into its intestine-absorbable form by the gut microbiota. Sci Rep 5, 12155 (2015). https://doi.org/10.1038/srep12155
20. Cui HM, Zhang QY, Wang JL, Chen JL, Zhang YL, Tong XL. Poor permeability and absorption affect the activity of four alkaloids from Coptis. Mol Med Rep. 2015 Nov;12(5):7160-8. doi: 10.3892/mmr.2015.4288. Epub 2015 Sep 3
21. Chen W, Miao YQ, Fan DJ, Yang SS, Lin X, Meng LK, Tang X. Bioavailability study of berberine and the enhancing effects of TPGS on intestinal absorption in rats. AAPS PharmSciTech. 2011 Jun;12(2):705-11. doi: 10.1208/s12249-011- 9632-z. Epub 2011 Jun 3.
22. 22. Chen W, Fan D, Meng L, Miao Y, Yang S, Weng Y, He H, Tang X. Enhancing effects of chitosan and chitosan hydrochloride on intestinal absorption of berberine in rats. Drug Dev Ind Pharm. 2012 Jan;38(1):104-10. doi: 10.3109/03639045.2011.592531. Epub 2011 Jul 20.
23. Lv XY, Li J, Zhang M, Wang CM, Fan Z, Wang CY, Chen L. Enhancement of sodium caprate on intestine absorption and antidiabetic action of berberine. AAPS PharmSciTech. 2010 Mar;11(1):372-82. doi: 10.1208/s12249-010-9386-z. Epub 2010 Mar 17.
24. Fan D, Wu X, Dong W, Sun W, Li J, Tang X. Enhancement by sodium caprate and sodium deoxycholate of the gastrointestinal absorption of berberine chloride in rats. Drug Dev Ind Pharm. 2013 Sep;39(9):1447-56. doi: 10.3109/03639045.2012.723219. Epub 2012 Oct 1.
25. Xu X, Yi H, Wu J, Kuang T, Zhang J, Li Q, Du H, Xu T, Jiang G, Fan G. Therapeutic effect of berberine on metabolic diseases: Both pharmacological data and clinical evidence. Biomed Pharmacother. 2021 Jan;133:110984. doi: 10.1016/j.biopha.2020.110984. Epub 2020 Nov 10.