When I started my AvalonX line, I knew berberine would be an inevitable piece of the unfolding picture! I first started experimenting with Berberine in 2018, when I started wearing a continuous glucose monitor (CGM). I found berberine effectively reduced my fasting blood sugar levels, as well helped my finicky IBS issues. I was taking the Thorne brand consistently, and after switching to my AvalonX Berberine 500, I have found a shocking average 20 point reduction in my postprandial blood sugar levels! I'm honestly a bit in shock! It's fascinating to experience such a measurable effect, in such a short amount of time. (Get 10% off AvalonX Berberine 500 with the code melanieavalon)
The Berberine Basics
Berberine is a natural plant alkaloid that has been used since 3000 BC, historically in Chinese and Ayurvedic herbal medicine to treat infection and intestinal inflammation. It colloquially rose to fame in modernity due to its potent blood sugar regulating potential, as high blood sugar levels are a key factor in metabolic syndrome, and the defining factor of pre-diabetes and diabetes. In addition to its antidiabetic properties, berberine boasts an array of benefits, including anti-inflammatory, anti-obesity, antimicrobial, and lipid modulating potential, without many of the side effects common to pharmaceuticals. Due to its potential to stimulate the AMPK pathway and autophagy, and function as an antioxidant, berberine has even been proposed as an anti-aging compound.
Blood Sugar Control
Today, berberine is most known for its blood sugar modulating power, with studies showing it may rival the effects of the pharmaceutical metformin. While metformin and other like-minded pharmaceuticals feature an array of potential side effects (gastrointestinal discomfort from metformin; cardiovascular damage, weight gain, and hypoglcemia from sulfonylureas; and increased risk of distal bone fractures, bladder cancer, and edema in postmenopausal women from pioglitazone), berberine has been used safely in traditional medicine for eons. It also does not have the contraindications of metformin, such as diabetics with liver disease, renal impairment, or cardiopulmonary insufficiency.
Berberine exhibits minimal if any side effects and a 2008 13 week study found any side effects (minor gastrointestinal issues) only occurred when berberine was used in combination with pharmaceuticals, and only during the initial 4 weeks of treatment. As the study noted, “None of the patients suffered from severe gastrointestinal adverse events when berberine was used alone. In combination-therapy, the adverse events disappeared in one week after reduction in berberine dosage. The data suggest that berberine at dosage of 0.3 g t.i.d. is well tolerated in combination-therapy.”
As for combination therapy, many trials have found pharmaceuticals are more effective at reducing blood sugar levels and beneficially affecting diabetic symptoms, when used in junction with berberine. As noted in a 2017 study, “It is postulated that the synergism action of berberine and metformin is attributed to similar anti-diabetic mechanisms in spite of different transporter and metabolism. Therefore, combination of these two drugs might allow reduction in dosage of each individual drugs to solve problems such as oral bioavailability of berberine and side effects of each alone.” These similar mechanisms may involve pathways such as AMPK, MAPK, PKC, PPARα, and PPARγ.
Berberine was first studied for these antidiabetic effects in 1986. In a 2008 study of 35 patients with type diabetes, berberine’s blood sugar lowering effects were found to be comparable to metformin, decreasing hba1c by 7.5%, fasting glucose by 6.9%, and postprandial glucose by 11.1%, as well as insulin levels. These finds were supported in a similar trial in 2010.
A 2015 metanalysis of berberine in 21 studies, found berberine beneficially affected Type 2 diabetes, compared to other regimens.
Many mechanisms have been proposed for berberine’s favorable effects on blood sugar. It can
directly discourage the intestine’s digestion and absorption of glucose, by inhibiting an intestinal enzyme called α-Glucosidase, which digests carbs and converts them into simpler forms called monosaccharides. Berberine can also increase glucose transporters around the body, helping the liver, fat, and muscle to remove glucose from the bloodstream. And within the bloodstream, berberine encourages peripheral cells to burn glucose.
The liver is actually the primary contributor to high resting blood sugars. Within the liver, berberine reduces the creation of new glucose (a process called gluconeogenesis), by reducing enzymes which create glucose, such as phosphoenolpyruvate carboxyl kinase and glucose-6-phosphatase. While studies have shown berberine increases insulin sensitivity, rodent studies indicate berberine may not affect insulin pathways in the liver, meaning berberine likely directly inhibits glucose formation in the liver, independent of insulin.
Berberines’ antimicrobial action in the gut may also contribute to its blood sugar lowering effects, and some researchers even hypothesize berberine may treat diabetes by affecting the gut microbiome, as chronic low level inflammation created by gut dysbiosis (due to antigen load and endotoxin byproducts of bacteria known as lipopolysaccharide), may encourage the formation of type 2 diabetes. More on that in a bit!
Berberine may also suppose glucose homeostasis by reducing oxidative stress, specifically by affecting proinflammatory cytokines and antioxidant enzymes. Studies have found berberine can increase glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and glutathione (GSH) in diabetic animals.
Berberine’s earliest use was to treat infections and inflammation within the GI system, which we now know works in part by reducing damage to the intestine inflicted by the aforementioned LPS. (LPS is often the primary role of death in sepsis, itself due to an imbalanced immune response to infection.) Berberine may reduce this damage by suppressing inflammatory cytokines and signaling molecules within the gut, such as NF-κB and MAPK, and by modulating the ApoM/S1P and Wnt/Beta-Catenin signaling pathways.
Berberine can also reduce inflammatory macrophages in the GI system. Macrophages are a pivotal part of the immune system which respond to invaders, and which can become detrimental to the host if they become chronically activated, or overly inflammatory.
Berberine has also been found to be directly antibacterial against E coli and Clostridium difficle, and consequently can prevent diarrhea in humans. These effects on certain types of the Clostridium species also can have the downstream effect of beneficially affecting bile acids, glucose, and lipids.
Berberine may support intestinal integrity by modulation bacteria species such as Phascolarctobacterium, Anaerotruncus, and Oscillibactea, and encourage bacteria which produces short chain fatty acids (SCFAs) such as butyrate. SCFAs can reduce inflammation, support the gut barrier, discourage pathogenic organisms, upreguakte GLP-1 and PYY, and enter the bloodstream to reduce blood sugar and lipid levels, all of which encourage metabolic health, and may help prevent obesity, insulin resistance, and other metabolic issues.
Also on the metabolic issue front, high branched chain amino acid (BCAA) levels have been associated with metabolic issues, and berberine has been shown to reduce BCAA-producing bacteria, such the Streptococcaceae, Clostridiaceae, and Prevotella families.
Berberine bears a fascinating benefit in its ability to favorably modulate adipose tissue (body fat) into a more healthy composition. The 3 main types of body fat include the relatively benign subcutaneous fat found beneath the skin (the stuff you can pinch), and the more inflammatory visceral fat surrounding organs and ectopic fat within organs. Berberine has been shown to encourage body fat recomposition, featuring less visceral fat. It may do this in part, and also provide long term weight loss effects, by changing gene expression in fat tissues to encourage a more consistent state of fat burning in the cell (specifically by encouraging AMPK-mediated ATGL expression). Berberine has also been found to upregulate thermogenesis in brown and white adipose tissue: basically the wasting of energy to create heat within the cell.
In mice studies, berberine actually reduces inflammation within fatty tissue, by preventing inflammatory macrophages from infiltrating the fatty tissue and building up within the fat tissues’ extracellular matrix, or ECM. As the researchers noted in a 2016 study, “Our findings imply that berberine improves insulin resistance by inhibiting M1 macrophage activation in adipose tissue.”
Also in rodent trials, berberine has been found to actually encourage the shrinking of fat cells, and reduce the number and size of the fat droplets within. It may do this in part by affecting critical transcription factors required for their formation. As noted in a 2006 study, “These studies suggest that BBR works on multiple molecular targets as an inhibitor of PPARgamma and alpha, and is a potential weight reducing, hypolipidemic, and hypoglycemic drug.”
Berberines metabolic effects are truly impressive. In addition to the many metabolic benefits from berberine’s effect on gut bacteria, berberine may inhibit Oscillibacter, which increses ZO-1 mRNA to reduce obesity. A 2020 review of 5 studies encompassing 1078 women found berberine could induce a redistribution of adipose tissue, reduce VAT in the absence of weight loss and improved insulin sensitivity, and improve lipids, discussed next!
Cholesterol And Lipids
Berberine has been found to provide potent anti-hyperlipidemic effects, beneficially modulating blood lipid levels. It can reduce fatty acid synthesis in the liver, as well as fatty liver itself. (In rodent trials, berberine has been found to inhibit NAFLD in mice fed a high fat diet, and human trials have found berberine supplementation may reduce liver enzymes in patients with type 2 diabetes.) It may do this in by part by reducing transcription factors like FoxO1, carbohydrate responsive element-binding protein (ChREBP), and sterol regulatory element-binding protein 1c (SREBP1). Berberine may also promote the liver’s mRNA expression to beneficially modulate LDL levels.
Other mechanism of action include directedly reducing levels of lipids into circulation from the intestines, as well as encouraging the production of butyrate, which can in turn beneficially affect lipid level. Berberine has also been shown to inhibit the creation of cholesterol and triglycerides in human hepatoma cells and hepatocytes.
In mice, berberine has been found in to protect against high fat diet, preventing insulin resentence and hyperlipidemia, and consequently protecting the liver.
A 2013 study in 144 patients found that berberine lead to weight loss and reductions of
total cholesterol, triglycerides and LDL cholesterol , while increasing HDL cholesterol. The patients experienced these effects in direct relation to taking the berberine, with the corresponding improving and worsening of biomarkers, when taking berberine, implementing a washout period, and then resuming, compared to placebo. The study concluded that “Berberine is effective and safe to mildly improve lipid profile in subjects with low risk for cardiovascular disease.”
Longevity & AMPK
AMPK is a fuel-sensing enzyme which plays a key role in energy use in the body, and which is activated by stressors such as calorie restriction, fasting, and exercise. Many of the benefits of fasting and exercise are, in fact, often attributed to AMPK upregulation, which can support the mitochondria, stimulate cellular repair and stem cell renewal, and reduce insulin resistance, inflammation, and other inflammatory processes.
Berberine has been found to be a potent stimulator of AMPK, which may be a key factor in how it can improve the aforementioned metabolic disorders, including type 2 diabetes, obesity, and dyslipidemia. Coupled with its downregulation of inflammatory gene expression, including TNF-α, IL-1β, and IL-, it’s no wonder berberine has been posited as a longevity compound.
Other Health Benefits
Berberine boasts a myriad of other potential health benefits. Berberine may have a beneficial effect on the immune system thanks to many factors, including beneficially affecting intestinal immune cells (70% of which are found in the gut), as well as immune factors. It can prevent the expression of inflammatory interleukins, macrophages, and tumor necrosis factor (TNF), and discourage low level inflammation.
When it comes to women, berberine has been found in humans to favorably affect fertility and live birth rates, by improving insulin resistance in theca cells and ovulation rates.
One of berberine’s more promising areas of further study, is its anticancer potential. These proposed mechanism include inhibition of cancer cell proliferation, suppressing cancer cell metastasis, instigating cancer cell death (apoptosis), encouraging autophagy, and synergistically upregulating the effects of anticancer pharmaceuticals.
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Anticancer Effects and Mechanisms of Berberine from Medicinal Herbs: An Update Review
Protective effect of berberine against LPS-induced injury in the intestine: a review
Berberine suppresses proinflammatory responses through AMPK activation in macrophages
Berberine improves lipid dysregulation in obesity by controlling central and peripheral AMPK activity
Rhizoma Coptidis and Berberine as a Natural Drug to Combat Aging and Aging-Related Diseases via Anti-Oxidation and AMPK ActivationAMPKα1-LDH pathway regulates muscle stem cell self-renewal by controlling metabolic homeostasiAMPK and the biochemistry of exercise: Implications for human health and diseaseAMPK and the biochemistry of exercise: Implications for human health and diseaseApplication of Berberine on Treating Type 2 Diabetes MellitusEfficacy of berberine in patients with type 2 diabetes mellitusBerberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression
Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension
Berberine Improves Glucose Metabolism in Diabetic Rats by Inhibition of Hepatic Gluconeogenesis
Efficacy of Berberine in Patients with Type 2 Diabetes
Berberine Relieves Metabolic Syndrome in Mice by Inhibiting Liver Inflammation Caused by a High-Fat Diet and Potential Association With Gut Microbiota
Berberine and lycopene as alternative or add-on therapy to metformin and statins, a review
Berberine inhibits 3T3-L1 adipocyte differentiation through the PPARgamma pathway
Polycystic ovary syndrome management: a review of the possible amazing role of berberine
Metformin and berberine, two versatile drugs in treatment of common metabolic diseases
Biological Activity of Berberine—A Summary Update
Application of Berberine on Treating Type 2 Diabetes Mellitus
Effects of Berberine on the Gastrointestinal Microbiota
Berberine increases adipose triglyceride lipase in 3T3-L1 adipocytes through the AMPK pathway
Berberine activates thermogenesis in white and brown adipose tissue
Berberine Regulated Gck, G6pc, Pck1 and Srebp-1c Expression and Activated AMP-activated Protein Kinase in Primary Rat Hepatocytes
Effects of berberine on lipid profile in subjects with low cardiovascular risk
Metformin and berberine, two versatile drugs in treatment of common metabolic diseases
Efficacy of Berberine in Patients with Type 2 Diabetes