Introduction: Exploring the use of berberine as hepatoprotective and glucose metabolism support.
Most of the food we eat is broken down in the body into sugar also called glucose. The liver and pancreas work together to help regulate the blood sugar levels in the body, known as glucose metabolism. The liver produces, stores, and releases glucose based on the body’s needs, which is instructed by the hormone glucagon and insulin produced by the pancreas. When glucose levels rise in our bodies, it signals the pancreas to produce more insulin. When this happens to the body, the pancreas must work harder and try to keep up with the demand. Over time this can lead to the development of type 2 diabetes where the body cannot regulate blood sugar levels. Type 2 diabetes is where the body has become insulin resistant, or the pancreas does not produce enough insulin.
According to the CDC, about 90-95% of people with diabetes have type 2 (CDC, 2022). When high blood sugar levels remain in the bloodstream or type 2 diabetes is left untreated, this can also lead to kidney disease, heart disease, and vision loss. Poor liver health is related to poor pancreas health, which leads to poor overall health.
Diabetes: An American Epidemic
According to the World Health Organization, diabetes was the ninth leading cause of death with an estimated 1.5 million deaths directly caused by diabetes (WHO, 2022). According to The American Diabetes Association, diabetes is a growing epidemic with 32 million Americans already having diabetes and 88 million more having pre-diabetes (ADA, 2022). According to the American Cancer Society, about 62,000 people will be diagnosed with pancreatic cancer in 2022 and about 49,000 will die of pancreatic cancer (American Cancer Society, 2022). Also, according to the American Cancer Society pancreatitis and type 2 diabetes are common risk factors for pancreatic cancer. Liver diseases like fatty liver and cirrhosis can also cause the body to become insulin resistant and unable to use insulin properly. There is an increasing amount of research showing the correlation between diabetes and pancreatitis. In a meta-analysis, cohort study, diabetes has been shown to be an increased risk of acute pancreatitis (Aune et al., 2020).
The need for more research is demonstrated in the ongoing trials for cardiovascular disease safety in antidiabetic drugs (Aldossari K. K., 2018). Several antidiabetic drugs may have an increased risk of cardiovascular complications and recent research shows that long-term antidiabetic drugs increase the risk of cancer compared to diabetics who do not use them (Liu et al., 2019). According to the American College of Cardiology, several new hypoglycemic medications are being studied for their effects on cardiovascular disease because cardiovascular disease is the leading cause of death among patients with diabetes (American College of Cardiology, 2022). The numbers and statistics reported by the CDC, WHO, ADA, and the American Cancer Diabetes Association make for a compelling case to find alternatives and more resources to help fight the spread of diabetes and liver diseases.
What is Berberine?
Berberine is a natural compound found in certain plants, including goldenseal, barberry, and Oregon grape. It has been used in traditional medicine for centuries and has been studied for its potential health benefits, including its ability to lower blood sugar and cholesterol levels. Berberine can be obtained from supplements, which are available at most health food stores.
In more specific terms, Berberine is an isoquinoline alkaloid and is said to have many pharmacological actions such as antibacterial, hypoglycemic, anti-inflammatory, anti-fibrosis, anti-cancer, and oxidation resistance (Zhou et al., 2020). Berberine, extracted from Coptis Root, has been frequently used for the adjuvant treatment of type 2 diabetes mellitus, hyperlipidemia, and hypertension in China for years (Lan et al., 2014). This review will investigate these studies to show the effects of berberine on the liver and the body and also berberine’s effect on the body’s regulation of glucose metabolism.
What are the Benefits of Berberine?
Here are some potential benefits of Berberine for various health conditions:
Weight Loss: Berberine has been shown to help promote weight loss by increasing metabolism, reducing insulin resistance, and decreasing fat storage.
Hormone Imbalance: Berberine can help regulate hormones such as insulin, estrogen, and testosterone. It has been studied for its potential to improve symptoms of conditions such as polycystic ovary syndrome (PCOS) and metabolic syndrome.
Anti-inflammation: Berberine has anti-inflammatory properties, which can help reduce inflammation in the body and may benefit conditions such as arthritis and inflammatory bowel disease.
PCOS Treatment: Berberine may be beneficial for women with PCOS, as it has been shown to improve insulin resistance and menstrual cycle irregularities. It may also help reduce symptoms such as hirsutism (excess hair growth) and acne.
Other potential benefits of berberine include:
Improved heart health by reducing cholesterol levels and blood pressure
Enhanced immune function by reducing inflammation and boosting white blood cell activity
Improved gut health by reducing inflammation and promoting the growth of healthy gut bacteria.
It's important to note that while berberine has shown promise for various health conditions, more research is needed to fully understand its effects and potential side effects. It's essential to work with a healthcare provider to determine if berberine is appropriate for your individual needs and to ensure safe and effective use.
Research Suggests The Powerful Benefits of Berberine
Berberine is said to reduce the risk of glucose intolerance, inflammation, oxidative stress, and liver diseases.
Methods
Databases searched for this review included PubMed, Google Scholar, and Cochrane Library. Terms used for this narrative review included berberine and liver, berberine and hepatoprotective, and berberine and diabetes. These search terms were used because this review focuses on the effects of berberine on the liver and glucose metabolism. The time period searched was from January 2008 to June 2022. The search included berberine and diabetes produced 78 results in Cochrane Library and 68 results in PubMed. The search of berberine and liver produced 62 results in PubMed and 56 results in Cochrane Library. The search of berberine and hepatoprotective produced 6 results in PubMed and 2 results in Cochrane Library. The search of berberine and liver produced 19,400 results in Google Scholar. Berberine and diabetes produced 18,600 results in Google Scholar and berberine and hepatoprotective produced 8,700 results. The search was narrowed using these terms because of the extensive research published about berberine’s effect on the body and glucose metabolism. The search did not include berberine alone as this would have been too broad.
Clinical Trials Discussion
A review of a randomized, parallel-controlled, clinical trial showed effective results for the use of berberine as a hepatoprotective supplement (Yan et al., 2015). This trial was conducted in three medical centers with a total of 184 eligible patients with non-alcoholic fatty liver disease. These patients were enrolled and randomly divided into; lifestyle intervention (LSI), LSI plus pioglitazone (PGZ) 15mg per day, and LSI plus BBR 0.5g three times a day, respectively, for 16 weeks. Berberine improved Non-Alcoholic Fatty Liver Disease and related metabolic disorders. The therapeutic effect of Berberine on NAFLD may involve a direct regulation of hepatic lipid metabolism (Yan et. al., 2015). According to the calculation of sample size for studies using t-TESTS, this randomized control trial was a larger trial compared to the other studies, conducted in this review (Elmore et al., 2020). This trial had a sufficient participation rate which showed the effectiveness of berberine. This trial of 16 weeks also showed a practical analysis of inadequate time. Although this trial showed effective results in 16 weeks, to fully understand the functions of berberine on a long-survival disease such as NAFLD, research would be needed for a much longer period.
Short-Term Experimental Research With Multiple Flaws
Published in the Nutrition Journal dated April 1, 2015, was research showing the short-term effects of a combined nutraceutical on insulin sensitivity, lipid level, and indexes of liver steatosis (Cicero, et al., 2015). This double-blind, placebo-controlled, randomized clinical trial was carried out in 40 moderately hypercholesterolemic subjects with metabolic syndrome. The study consisted of a cross-over designed trial of 18 weeks of diet stabilization in which patients received standard behavioral and qualitative dietary suggestions to correct unhealthy eating habits. The aim of the study was to evaluate the short-term metabolic effects of a combined nutraceutical containing berberine and chlorogenic acid on overweight subjects with mixed hyperlipidemia.
The numerous flaws of this study started with the very small sample size with regard to the cross-over design of the trial. The sample size was 40 subjects in total and then the sample was divided into two more groups consisting of nutraceutical and diet treatment as opposed to the placebo diet group. The disadvantage of this randomized control trial was the external validity. It may be unclear what population is represented by the remaining people in a randomized control trial once the study groups have been constructed and the various possible participants have been eliminated according to the research's exclusion criteria (Elmore et al., 2020).
Although longer than all the other trials in this review, the short duration of this trial, should have a follow-up with a minimum of 6 months to a year for a thorough analysis. The third flaw was the general dietary suggestions based on not overeating as opposed to a more strict uniform guideline. Both groups experienced a significant decrease in body weight, BMI, and waist circumference without significant differences between the treatments. The fourth flaw of the study was not evaluating the degree of liver steatosis, this is a common flaw in all the trials within this review.
Human Body’s Ability To Digest Suggests More Research
In a Chinese review of the biological properties and clinical applications of berberine published in 2020, berberine showed to improve various diseases including digestive diseases, cardiovascular diseases, cancer, and metabolic disorders (Song et al., 2020). The glucometabolic use of berberine showed positive results in humans but the lipid metabolism trials were done on rats. The metabolic disorders referenced within this review researched only rat trials and included none on humans. According to neuroscientist, Denes V. Agoston the basal metabolic rate of a rat is 6.4 times faster than humans (Agoston, 2017). This would be insufficient evidence showing the effectiveness of berberine on metabolic disorders in humans, these studies should be done on humans as were in other trials within this review.
Beneficial Metabolic Effects From Berberine Supplementation
Berberine showed good and promising results in a recently published review of its therapeutic effects on metabolic diseases (Xu et al., 2021). A great advantage of this review was the extensive research referencing 60 different trials. Upon looking at this review it is noticeable that the studies it references are smaller compared to the RCT done by Yan et al., 2015. This review had sample sizes ranging from 12 to 60 compared to the 187 sample sizes done by Yan’s control trail. This review had 1 trial with 100 participants, but this study was singular and had almost double the participants compared to the other studies within the review. The duration of these studies ranged greatly from 1 month to 6 months. These times all showed the benefits of berberine as a hepatoprotective and glucose metabolism supplement. The one-month studies are insufficient time especially compared to the other trials.
Lower Blood Sugar Levels Accomplished: More Research Suggested On Diverse Ethnic Groups
In a pilot study published in 2008, berberine showed to significantly decrease HbA1c levels in diabetic patients (Yin et al., 2008). 74 Chinese patients successfully participated in this study, one group received berberine and the other received metformin in a 3-month trial. While both groups saw a decrease in their HbA1c, functional liver or kidney damage was not observed for all patients. To complete the functionality against metformin, liver and kidney status would need to be monitored and 3 months would not be sufficient time to show the complete function. Another disadvantage of this study was the undiversified ethnic group. This study was done on Chinese patients alone. To fully understand the success of berberine on diabetes a more diverse ethnic population would need to be studied.
Trial Presents Berberine Benefits To Treat Diabetes Patients Despite Trial Flaws
A phase 2 randomized control trial of berberine on patients with fatty liver disease and type 2 diabetes showed improvement in glycemic metabolism and liver function (Harrison et al., 2021). One group of 100 obese patients was treated with berberine and heavily treated with other agents both before and during the study period of this 90-day trial. The first flaw of this study was the other agents were accounted for and could also influence glycemic metabolism and liver function results. Compared to the other trials reviewed this 90-day trial is not sufficient for a thorough analysis. 51 subjects completed the trial, and the treatment codes and datasets were not publicly available to analyze making this study questionable. The results were not shared with the sponsors or investigators and the sample size decreased significantly. Another flaw of this study was the safety set consisted of subjects receiving just one dose of the study treatment and missing data was said to be accounted for. This trial also states conflicts of interest with numerous pharmaceutical drug companies and grants research support. In general, these trials only publish studies that show results that are favorable to them.
Promising Results of Berberine as an effective Supplement for Glucose Metabolism And Liver Protection
In the future, more research and in-depth clinical studies are needed to support the clinical application of berberine. This review did show promising results of berberine as an effective supplement for glucose metabolism and liver protection. In the study published in Theranostics, it was discovered that berberine showed low bioavailability due to its poor oral absorption and extensive metabolism as the main obstacles to the practical application of this plant as a supplement (Feng et al., 2019).
In the course of medical treatment, many challenges emerge such as medication resistance. Metabolic and liver diseases are chronic illnesses that require long-term ongoing management. Therefore, evidence from further clinical research should be conducted, especially long-term studies. None of these trials were done for longer than 6 months. A thorough understanding of berberine for the use of liver protection would require more time.
Learn More About The Beneficial Effects of Traditional Chinese Medicine
The purpose of this article is to educate about the potential beneficial effect and potential adverse effects of using a natural plant product such as Berberine to treat human subjects dealing with various health problems. As mentioned prior, this objective analysis of trials and research does incentivize improved systematic reviews, as the evidence suggests there are flaws in health markers.
Discuss The Beneficial Effects of Implementing Herbal Medicine With A Board-Certified Physician
Berberine can be taken in supplement form, typically in capsule or tablet form. The recommended dosage can vary depending on the individual's health needs and the specific brand of supplement. It's important to consult with a healthcare provider or a certified practitioner to determine the appropriate dosage and ensure the safe and effective use of berberine. They can also advise on potential interactions with other medications and supplements. It's also essential to follow the manufacturer's instructions and only purchase supplements from reputable sources.
Despite these challenges at Eastern Acupuncture And Wellness, we are delighted to know and share the increase in clinical trials in relation to Traditional Chinese Medicine. We encourage you to learn more about what Herbal Medicine and Traditional Medicine can do for you. You can do this by meeting with one of our Board Certified Chinese Medicine Doctors in person or online. As a new patient, you can claim a Complimentary 20 Minute Consultation with our licensed specialists.
If you prefer to learn by reading about the subject, we welcome you to continue accessing our educational blog regarding these wellness topics and more. In our blog, you will see that we discuss:
Weight loss
Positive lifestyle changes
How to improve blood sugar levels
The anti-inflammatory effects of TCM
Other natural ways to treat diabetes
Effective ways to treat PCOS
And more Integrative Medicine topics!
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About The Author of This Narrative Review
Dr. Lisa Shields | Herbal Medicine and Acupuncture Physician at Eastern Acupuncture And Wellness
Lisa Shields graduated from Oregon College of Oriental Medicine with her master’s degree. She then received her doctorate degree from the Pacific College of Oriental Medicine. She is licensed in acupuncture and herbal medicine by the National Certification Commission for Acupuncture and Oriental Medicine (NCCAOM) and the Oregon and Florida medical board. Learn more about the specialties and background of Dr. Lisa Shields by visiting her practitioner profile here.
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