By Kim Ross, DCN, CNS, LDN, IFMCP⁺

Berberine and Blood Sugar: Unlocking Clinical Potential with Enhanced Absorption

1. Introduction to Berberine
2. Berberine and Insulin Signaling and Glucose Metabolism
3. Bioavailability and Absorption Concerns
4. Pure Encapsulations Nutrient Solutions
5. Conclusion
6. Resources

Introduction to Berberine

Berberine is a bioactive isoquinoline alkaloid found in several botanicals, including barberry (Berberis vulgaris), Oregon grape (Berberis aquifolium), Indian barberry (Berberis aristata), Chinese goldthread (Coptis chinensis) and goldenseal (Hydrastis canadensis). Its oldest use dates back to 3000 BC,1 though it has been more commonly used for over 400 years as a traditional therapeutic agent in China, India and the Middle East and offers a wide array of health benefits.²

Researchers are interested in berberine for its capacity to reduce oxidative stress, modulate cytokine production, suppress adipogenesis and lipid accumulation, provide neuroprotection, restore the gut microbiome and regulate glucose metabolism and insulin signaling.^2,3

One key challenge of administering berberine is oral bioavailability. These pharmacokinetic constraints have driven the development of enhanced delivery systems. Among these, phytosome formulations have been investigated to improve absorption and clinical performance. Recent work has demonstrated improved pharmacokinetic profiles for food-grade berberine formulations.⁴ Randomized trials of berberine phytosome have reported favorable metabolic effects compared with standard preparations.⁵

This blog will focus on how berberine supports glucose metabolism and the clinical importance of choosing the right formulation to enhance absorption in your patients.

Berberine and Insulin Signaling and Glucose Metabolism

Berberine's clinical effects on glucose metabolism and insulin signaling are shaped by its pharmacological behavior. Although oral absorption is limited (less than 1%), berberine and its active metabolites primarily concentrate in the liver to govern glucose production and utilization.¹ Within the liver, berberine influences pathways that regulate gluconeogenesis. After entering circulation, berberine is rapidly and widely distributed to muscle, lung, brain, heart, pancreas, adipose and kidney tissue.¹

Mechanisms of Action

Berberine influences multiple, interconnected aspects of metabolic health, which helps explain its broad clinical relevance:

Glucose metabolism: Berberine affects glucose metabolism by stimulating glycolysis, the fundamental metabolic process for energy production. It also impacts gluconeogenesis, which is important since altered gluconeogenesis contributes to changes in fasting glucose states and insulin signaling. Furthermore, berberine enhances the production of GLP-1, thereby improving insulin signaling.²

Insulin signaling: After insulin is produced by the b-cells of the pancreas, it binds to insulin receptor sites on the cell surface. This process activates a chain reaction within the cell, known as the insulin signaling cascade. Insulin receptor substrate 1 (IRS-1) and protein kinase B (PKB, also known as Akt) are key messengers within cells. This promotes the translocation of the glucose transporter 4 (GLUT-4) protein to the cell surface, allowing glucose to be shuttled into the cells.

Berberine has been reported to have an impact on several areas of this chain reaction:

1. It reduces the inhibitory signal of IRS-1, thereby improving intracellular communication.⁶
2. It enhances Akt signaling and improves cellular glucose uptake.⁶
3. It promotes the movement of GLUT4 transporters to the cell surface. This enhances the ability of skeletal muscle cells to absorb glucose from the circulation and store it as glycogen, thereby improving whole-body glucose utilization.⁷
4. It activates AMP-activated protein kinase (AMPK), a central "energy sensor" in cells. AMPK activation redirects metabolism toward energy-efficient pathways, promoting glucose uptake and utilization while inhibiting processes that contribute to excess glucose production.^2,8 Further, there is an increased expression of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1), a key regulator of mitochondrial biogenesis.⁹
5. Berberine also upregulates SIRT1, a key regulator in adipose tissue, that contributes to insulin signaling, as well as promotes insulin secretion from b-cells.⁷

BERBERINE’S IMPACT ON INSULIN SIGNALING AND GLUCOSE METABOLISM

Additionally, berberine has an impact on other key mechanisms of action, including:

Lipid balance: Berberine reduces the liver's tendency to produce new fats from excess carbohydrates (a process known as de novo lipogenesis) and promotes fat burning for energy. Clinically, this supports fat metabolism within liver cells.¹⁰

Gut microbiota interaction: Berberine directly influences the gut microbiome in several ways. It encourages growth of beneficial bacteria, modulates the intestinal barrier and increases the production of bile acids (BA), short-chain fatty acids (SCFA), dopamine and branched-chain amino acids (BCAA), while reducing the production of trimethylamine (TMAO).¹¹

Healthy cytokine balance and antioxidant support: It has been reported that berberine supports healthy cytokine balance, inhibits leukocyte adhesion, suppresses oxidative stress and promotes immune regulation.^2,12

Notably, one study identified 22 pathways and molecular mechanisms that berberine impacts for glucose regulation alone, underscoring the depth of this topic, which extends beyond the scope of this blog.¹³

Phytosome^™ Technology for Increased Absorption

Phytosomes, also referred to as herbasomes, protect herbal extracts from digestive fluids and intestinal microbes, allowing them to enter the bloodstream, prolong circulation and delay clearance.²⁰ Phytosome^™ technology combines a botanical extract with phospholipids, improving membrane affinity, lymphatic uptake and resistance to P-gp efflux, which together enhance oral absorption and systemic exposure at a given dose.⁴ For berberine, this strategy aims to deliver higher effective concentrations to the liver and muscle, which are central to gluconeogenesis control, GLUT4-mediated uptake and overall glucose homeostasis, while potentially reducing GI intolerance seen with conventional forms.

Evidence for Enhanced Delivery

Berbevis^® is a form of berberine that utilizes Phytosome^™ technology. A pharmacokinetic study utilizing Berbevis^® showed significantly improved plasma exposure versus conventional berberine (chloride), confirming better absorption with the phospholipid complex.⁴ This led to further research, including:

• A double-blind, placebo controlled RCT reported that Berbevis^® (550 mg, twice daily) promoted healthy glycemic control and insulin signaling over placebo, while also supporting healthy lipid profiles.⁵
• Additional studies support similar promotion of healthy lipid profiles and cardiometabolic risk factors with Berbevis^® at a single dose of 500 mg per day.^21,22
• Two other studies using 550 mg twice daily of Berbevis^® reported support for healthy glucose metabolism and insulin signaling, with one study also showing significant support for cardiometabolic parameters.^23,24

Taken together, these data indicate that formulation matters. A phytosome form of berberine increases exposure, improves tolerability and results in clinically meaningful improvements in endpoints related to insulin signaling and glucose regulation, potentially at lower total daily doses than conventional berberine.

Pure Encapsulations Nutrient Solutions

Berberine UltraSorb^™ provides Berbevis^®, which is manufactured from Berberis aristata root extract. This berberine phytosome provides enhanced bioavailability that promotes healthy glycemic control, helps maintain healthy glucose levels already within normal ranges and promotes healthy insulin receptor function and signaling.⁴ Berberine UltraSorb^™ provides 550 mg of clinically studied berberine phytosome that is four times more bioavailable than standard berberine.

Suggested Dose: As a dietary supplement, take 1 capsule 1 to 2 times daily, with or between meals.

Conclusion

Berberine, a natural alkaloid with a long history of medicinal use, continues to demonstrate strong clinical relevance in modern metabolic care. While its low oral bioavailability has historically limited application, advances such as Phytosome^™ technology now offer improved absorption and greater clinical utility at lower and better tolerated doses.

By targeting multiple pathways simultaneously, berberine provides a multifaceted approach to restoring metabolic balance. For clinicians, berberine phytosome represents a promising adjunctive option for patients to support their metabolic health, particularly when combined with foundational nutrition and lifestyle strategies.^‡

Resources

For additional information that includes diet and lifestyle recommendations for supporting glucose regulation and insulin signaling, refer to the resources listed below:

Cardiometabolic Support Protocol: Designed by our scientific and medical advisors to help you deliver the most effective care and support insulin signaling and glucose metabolism.

Berberine Webinar: Watch the webinar “Berberine Deep Dive: An Update to Evidence-Based Clinical Use for Cardiometabolic Applications^‡,” presented by Kelly Heim, Ph.D.

To learn more about the research on selected nutrient solutions, download the following:

• Berberine UltraSorb^™ Sales One Pager
• Berberine UltraSorb^™ Product Info Sheet

Drug-Nutrient Interactions Checker: Provides valuable information on potential interactions between your patients' prescriptions, over-the-counter medications and nutritional supplements.

PureInsight^™: Our streamlined platform easily collects patient data and provides valuable recommendations to help achieve their health goals.

Virtual Dispensary: Our Pure Patient Direct program provides account holders FREE access to our virtual dispensary to help simplify patient sales and reduce in-office inventory.

You can also explore Pure Encapsulations^® to find On-Demand Learning, Clinical Protocols and other resources developed with our medical and scientific advisors.

1. Khoshandam A, Imenshahidi M, Hosseinzadeh H. Phytother Res. 2022;36(11). doi:10.1002/ptr.7589
2. Utami AR, Maksum IP, Deawati Y. Biology (Basel). 2023;12(7). doi:10.3390/biology12070973
3. Och A, Och M, Nowak R, Podgórska D, Podgórski R. Molecules. 2022;27(4). doi:10.3390/molecules27041351
4. Petrangolini G, Corti F, Ronchi M, Arnoldi L, Allegrini P, Riva A. Evid Based Complement Alternat Med. 2021;2021. doi:10.1155/2021/7563889
5. Rondanelli M, Gasparri C, Petrangolini G, et al. Eur Rev Med Pharmacol Sci. 2023;27(14). doi:10.26355/eurrev_202307_33142
6. Li A, Lin C, Xie F, Jin M, Lin F. Metab Syndr Relat Disord. 2022;20(8). doi:10.1089/met.2022.0017
7. Lv X, Zhao Y, Yang X, et al. Front Pharmacol. 2021;12. doi:10.3389/fphar.2021.720866
8. Bellavite P, Fazio S, Affuso F. Molecules. 2023;28(11). doi:10.3390/molecules28114491
9. Qin X, Jiang M, Zhao Y, et al. Br J Pharmacol. 2020;177(16). doi:10.1111/bph.14935
10. Cai Y, Yang Q, Yu Y, Yang F, Bai R, Fan X. Front Pharmacol. 2023;14. doi:10.3389/fphar.2023.1283784
11. Cheng H, Liu J, Tan Y, Feng W, Peng C. J Pharm Anal. 2022;12(4). doi:10.1016/j.jpha.2021.10.003
12. Wang K, Yin J, Chen J, Ma J, Si H, Xia D. Phytomedicine. 2024;128:155258. doi:10.1016/j.phymed.2023.155258
13. Han Y, Xiang Y, Shi Y, et al. Evid Based Complement Alternat Med. 2021;2021. doi:10.1155/2021/9987097
14. Kwon M, Lim DY, Lee CH, Jeon JH, Choi MK, Song IS. Pharmaceutics. 2020;12(9). doi:10.3390/pharmaceutics12090882
15. Solnier J, Zhang Y, Kuo YC, et al. Pharmaceutics. 2023;15(11). doi:10.3390/pharmaceutics15112567
16. Liu CS, Zheng YR, Zhang YF, Long XY. Fitoterapia. 2016;109. doi:10.1016/j.fitote.2016.02.001
17. Feng X, Wang K, Cao S, Ding L, Qiu F. Front Pharmacol. 2021;11. doi:10.3389/fphar.2020.594852
18. Tan XS, Ma JY, Feng R, et al. PLoS One. 2013;8(10). doi:10.1371/journal.pone.0077969
19. Moon JM, Ratliff KM, Hagele AM, Stecker RA, Mumford PW, Kerksick CM Nutrients. 2022;14(1). doi:10.3390/nu14010124
20. Kalaivani, P, Kamaraj, R. Cureus. 2024;16(8):e68180. doi:10.7759/cureus.68180
21. Cesarone MR, Hu S, Belcaro G, et al. Minerva Gastroenterol. 2024;70(1). doi:10.23736/s2724-5985.23.03540-4
22. Cesarone MR, Hu S, Belcaro G, et al. Minerva Med. 2025;116(4):285-291. doi:10.23736/S0026-4806.25.09637-5
23. Di Pierro F, Sultana R, Eusaph AZ, et al. Front Pharmacol. 2023;14. doi:10.3389/fphar.2023.1269605
24. Rondanelli M, Riva A, Petrangolini G, et al. Nutrients. 2021;13(10). doi:10.3390/nu13103665

⁺Kim Ross is a paid consultant for Pure Encapsulations.

Magnesium: Forms, Functions and Evidence-Based Clinical Use

Presented by: Kelly Heim, PhD^*

Magnesium plays important roles in cardiovascular, neurocognitive, and mental health. Nearly half (48%) of Americans do not meet the estimated average requirement.1 Dietary supplements contain various forms of magnesium, which vary in bioavailability, cost and clinical uses. In this webinar, you will learn how to optimize magnesium effectively for specific health goals.^‡

Learning objectives:

• Understand key differences between 5 common forms of magnesium found in dietary supplements


• Recognize common pitfalls and best practices when assessing magnesium status


• Obtain up-to-date information on evidence-based uses, dosage, duration and monitoring to support cardiovascular, cognitive, and mental health.^‡


• Review contraindications and drug interactions

Building and Refurbishing Mitochondria For Cognitive, Muscular and Metabolic Health

Presented by: Kelly Heim, Ph.D.^*

Mitochondria generate the energy required for almost all physiological functions within the body and are essential for healthy cognition, muscle function and metabolism. In this webinar, pharmacologist Kelly Heim, PhD* will review the current state of the science and its clinical implications in neurocognitive, muscular and metabolic health.

Learning Objectives:

• Learn how healthy mitochondria contribute to brain, muscle and metabolic health


• Discover which types of exercise and dietary habits can enhance mitochondrial quality and quantity


• Review current evidence-based indications and condition-specific interventions that support mitochondrial health

Berberine Deep Dive: An Update on Evidence-Based Clinical Use for Cardiometabolic Applications‡

Presented by: Kelly Heim, Ph.D.^*
Updated November 2025

Berberine is an alkaloid that modifies the gut microbiome, mitochondria and cellular longevity pathways to elicit well-documented efficacy in metabolic and cardiovascular applications. Successful clinical use requires a basic comprehension of indications, dosing and pharmacological profile. Variable responses to supplementation have been partially ascribed to poor bioavailability, which can be overcome with enhanced delivery systems. In this webinar, you will learn how to use berberine effectively for the right patients and health goals.^‡

Learning Objectives:

• Review the clinical evidence on berberine and its effects on glucose and lipid metabolism^‡


• Obtain current dosing protocols and monitoring intervals for cardiovascular and metabolic health objectives^‡


• Recognize the key differences between berberine hydrochloride, sulfate and enhanced-absorption formulations


• Learn how to identify and manage potential interactions with metformin and other drugs

Weight Management: Why it Matters & What to Do About it^‡†

Presented by: Caroline Cederquist, M.D.

Thursday, February 25, 2021

Weight management constitutes an epidemic in the United States, with over 70% of Americans reporting a BMI of over 25.¹ Drawing from over 20 years of clinical experience, Dr. Cederquist will share her methods for supporting healthy weight management in her patients, from the obvious to the obscure.

Learning Objectives:

• Learn why weight management is crucial in all practices


• Discover new ways of looking at old problems with weight management


• Help your patients make sustainable changes by implementing new tools, tests, and unique methods