In this episode, Dr. Donohoe and Dr. Panno discuss two of the most commonly used interventions, both in mainstream medical and functional medicine fields, Metformin and Berberine. Dr. Panno recently wrote a paper on this topic where he read through numerous research articles in order to gain more clarity and understanding of these two products (how they work and how effective they are). We get into the science behind them but also the clinical takeaways and what it all means. Below we reference all the articles used. PLEASE SUBSCRIBE TO THE PODCAST For more Diabuddies content follow us on The Diabuddies Podcast Facebook page. Twitter: @TheDiabuddies Instagram: @thediabuddiespodcast You can email us at TheDiabuddiesPodcast@gmail.com Time Stamps 1:10 - Start/Introduction 6:25 - Berberine: What Does It Do And How Effective Is It? 16:30 - Where Does Berberine Come From? 22:45 - Where Does Metformin Come From? 31:30 - How Does Metformin Work? (MOA) 39:50 - How Does Berberine Work? (MOA) 44:10 - Can you take Metformin and Berberine Together? 57:30 - Burst My Beta Cells Resources/Links Discussed in the episode: References Arayne, M., Sultana, N., & Bahadur, S., (2007). The berberis story: berberis vulgaris in therapeutics. Park J Pharm Sci; 20(1): 83-92. PMID: 17337435 Bailey, C., & Day, C., (2004). Metformin: its botanical background. Pract Diabetes Int; 21: 115-117. https://doi.org/10.1002/pdi.606 Bailey, C., & Day, C., (1989). Traditional plant medicines as treatments for diabetes. Diabetes Care; 12(8): 553-564. PMID: 2673695 Center of Disease Control (2020). National Diabetes Statistic Report 2020, Estimates of Diabetes and its burden in the united states. Retrieved at: https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf Chang, W., Zhang, M., Li, J., Meng, Z., Wei, S., Du, H., Chen, L., & Hatch, G., (2013). Berberine improves insulin resistance in cardiomyocytes via activation of 5’adenosine monophosphate-activated protein kinase. Metabolism; 62(8): 1159-1167. PMID: 23537779 Chang, W., Chen, L., & Hatch, G., (2015). Berberine as a therapy for type 2 diabetes and its complication: from mechanism of action to clinical studies. Biochem Cell Biol; 93(5): 479-486. PMID: 19800084 Cheuh, W., & Lin, J., (2012). Protective effect of berberine on serum glucose levels in non-obese diabetic mice. International Immunopharmacology; 12(3): 534-538. PMID: 22266065 Choi, YH., & Lee, MG., (2006). Effects of enzyme inducers and inhibitors on the pharmacokinetics of metformin in rats: involvement of CYP2C11, 2D1, 3A1/2 for the metabolism of metformin. B J Pharmacol; 149(4): 424-30. PMID: 16940989 ClinCal (2020). The Top 200 Drugs of 2021. Medical Expenditure Panel Survey (MEPS). Retrieved at: https://clincalc.com/DrugStats/Top200Drugs.aspx Dong, H., Wang, H., Zhao, L., & Lu, F., (2012). Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis. Evidence Based complement alternative med; 2012: 591654. PMID: 23118793 Elbere, I., Kalnina, I., Silamikelis, I., Konrade, I., Zaharenko, L., Sekace, K., et al., Klovins, J., (2018). Association of metformin administration with gut microbiome dysbiosis in healthy volunteers. PLoS One; 13(9): e0204317. PMID: 30261008 Foretz, M., Herbrad, S., Leclerc, J., Zarrinpashneh, E., Soty, M., Mithieux, G., et al., & Viollet, B., (2010). Metformin inhibits hepatic gluconeogenesis in mice independently of LKB1/AMPK pathway via a decrease in hepatic energy state. The Journal of Clinical investigation; 120(7): 2355-2369. PMID: 20577053 Fullerton, M., Galic, S., Marcinko, K., Sikkema, S., Pulinikunnil, T., Chen, Z., et al., & Steinberg, G., (2013). Single phosphorylation sites in ACC1 and ACC2 regulate lipid homeostasis in the insulin-sensitizing effects of metformin. Nat Med; 19(12): 1649-1654. PMID: 24185692 Lan, J., Zhao, Y., Dong, F., Yan, Z., Zheng, W., Fan, J., & Sun, G., (2015). Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia, and hypertension. Journal of Ethnopharmacology; 16H: 69-81. PMID: 25498346 Le Bastard, Q., Grégoire, M., Chapelet, G., Javaudin, F., Dailly, E., Batard, E., Montassier, E., Al, G. G. A., & Knights, D. (2018). Systematic review: human gut dysbiosis induced by non‐antibiotic prescription medications. Alimentary Pharmacology & Therapeutics, 47(3), 332. PMID: 29205415 Li, Y., Wang, Y., Kong, W., Yang, P., Wang, Y., Li, Y., Yi, H., et al., & Jiang, J., (2011). Bioactivates of berberine metabolites after transformation throughout CYP450 isoenzymes. Journal of translational medicine; 9(62): 62. PMID: 21569619 Liang, Y., Xu, X., Yin, M., Zhang, Y., Haung, L., Chen, R., & Ni, J., (2019). Effects of berberine on blood glucose in patients with type 2 diabetes mellitus: a systematic literature review and meta-analysis. Endocrine Journal; 66(1): 51-63. PMID: 30393248 Lyu, Y., Zhang, Y., Yang, M., Lin, L., Yang, X., Cheung, S., et al., & Zuo, Z., (2019). Pharmacokinetic interactions between metformin and berberine in rats: Role of oral administration sequences and microbiota. Life Sciences; 235: 116818. PMID: 31473193 Mao, L., Chen, Q., Gong, K., Xu, X., Xie, Y., Zhang W., et al., & Zhang, Y., (2018). Berberine decelerates glucose metabolism via suppression of mTOR-dependent HIF-1α protein synthesis in colon cancer cells. Oncol Rep; 39(5). 2436-2442. PMID: 29565467 Miller, R., Chu, Q., Xie, J., Foretz, M., Viollet, B., & Birnbaum, M., (2013). Biguanides suppress hepatic glucagon signaling by decreasing production of cyclic AMP. Nature; 494(7436):256-260. PMID: 23292513 Neag, M., Mocan, A., Echeverria, J., Pop, R., Bocsan, C., Crisan, G., & Buzoianu, A., (2018). Berberine: Botanical Occurrence, Traditional Uses, Extraction Methods, and Relevance in Cardiovascular, Metabolic, Hepatic, and Renal Disorders. Front Pharmacology; 9: 557. PMID: 30186157 Owen, M., Doran, E., & Halestrap, A., (2000). Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondria respiratory chain. Biochem J; 348; 607-614. PMID: 10839993 Petersen, M., American Diabetes Association. Economic Costs of Diabetes in the U.S. in 2017. Diabetes care; 41(5): 917-928. PMID: 29567642 Pryor R., & Cabreiro F., (2015). Repurposing metformin: an old drug with new tricks in its binding pockets. Biochemical Journal; 471(3): 307-322. PMID: 26475449 Ren, G., Guo, J., Quian, Y., Kong, W., & Jiang, J., (2020). Berberine improves glucose and lipid metabolism in HepG2 cells through AMPKα1 activation. Front Pharmacology; 11: 647. PMID: 32457629 Yin, J., Xing, H., & Ye, J., (2008). Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism; 57(5): 712-717. PMID: 18442638 Yue, S., Liu, J., Wang, W., Wang, A., Yang, X., Guan, H., Wang, C., & Yan, D., (2019). Berberine treatment-emergent mild diarrhea associated with gut microbiota dysbiosis. Biomed Pharmacother; 116: 109002. PMID: 31154270 Zhang, H., Wei, J., Xue, R., Wu, J., Zhao, W., Wang, Z., et al., & Jiang, J., (2010). Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression. Metabolism; 59(2): 285-292. PMID: 19800084 Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., et al., & Moller, D., (2001). Role of AMP-activated protein kinase in mechanisms of metformin action. The Journal of Clinical Investigation; 108(8): 1167-1174. PMID: 27654259
