Berberine is a natural plant alkaloid that has been used since 3000 BC, historically in Chinese and Ayurvedic herbal medicine, to help manage infection and various intestinal conditions. It colloquially rose to fame in modernity due to its potent blood sugar-regulating potential, as elevated blood sugar levels may play a role in metabolic flexibility and function. In addition to supporting glucose uptake, berberine likely has other functional properties, 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.
Berberine has been used safely by traditional medicine for thousands of years, and is GRAS (generally recognized as safe). 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.”
Berberine Health Effects
Blood Sugar Control
Many mechanisms have been proposed for berberine’s blood sugar modulating power, as it has been shown to support blood sugar regulation for those within normal blood sugar ranges. It may directly discourage the intestine’s digestion and absorption of glucose by inhibiting an intestinal enzyme called α-Glucosidase, which digests carbohydrates 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. 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 may impede the creation of new glucose (a process called gluconeogenesis), by reducing enzymes that create glucose, such as phosphoenolpyruvate carboxykinase 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’ potential 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 the antigen load and endotoxin byproducts of bacteria (lipopolysaccharide, or LPS) may encourage the formation of type 2 diabetes.
Berberine may also support glucose homeostasis by reducing oxidative stress. Studies have found berberine can increase glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and glutathione (GSH) in diabetic animals.
Never use Berberine in combination with other diabetic medications without first discussing and consulting with your primary healthcare provider on any possible interactions.
Berberine’s earliest use was to treat infections and intestinal irritations within the GI system, which we now know works in part by reducing damage to the intestine inflicted by 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 signaling molecules within the gut, such as NF-κB and MAPK, and by modulating the ApoM/S1P and Wnt/Beta-Catenin signaling pathways.
Berberine may also balance macrophages in the GI system. Macrophages are a pivotal part of the immune system which respond to invaders and can become detrimental to the host if they become chronically activated.
Berberine may support intestinal integrity by modulating bacteria species such as Phascolarctobacterium, Anaerotruncus, and Oscillibactea, and encourage bacteria that produce short-chain fatty acids (SCFAs) such as butyrate. SCFAs may support the gut barrier and discourage pathogenic organisms, upregulate GLP-1 and PYY, and enter the bloodstream to modulate blood sugar and lipid levels, all of which encourage metabolic health.
Berberine bears a fascinating benefit in its ability to favorably modulate adipose tissue (body fat) into a healthier composition. The 3 main types of body fat include the relatively benign subcutaneous fat found beneath the skin, 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 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: the wasting of energy to create heat within the cell.
In mice studies, berberine has been shown to reduce 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 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.”
Berberine’s metabolic effects are truly impressive. In addition to the many metabolic benefits from berberine’s effect on gut bacteria, berberine may inhibit Oscillibacter, which increases 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 visceral adipose tissue in the absence of weight loss, and improve insulin sensitivity and lipids, discussed next!
Cholesterol And Lipids
While more research is needed, berberine has been found to provide potent anti-hyperlipidemic effects in subjects already in normal ranges, beneficially modulating blood lipid levels. It can reduce fatty acid synthesis in the liver, as well as the fatty liver itself. (In rodent trials, berberine has been found to inhibit NAFLD in mice fed a high-fat diet. It may do this in 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 mechanisms of action include directly reducing levels of lipids into circulation from the intestines, as well as encouraging the production of butyrate, which can in turn beneficially affect lipid levels. 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 to protect against a high-fat diet, preventing insulin resistance and hyperlipidemia, and consequently protecting the liver.
Longevity and AMPK
AMPK is a fuel-sensing enzyme that plays a key role in energy use in the body, and 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 and inflammatory markers.
Berberine has been found to be a potent stimulator of AMPK, which may be a key factor in how it may improve the aforementioned metabolic disorders. Coupled with its downregulation of inflammatory gene expression, including TNF-α and IL-1β, it’s no wonder berberine is considered a potential longevity-supporting 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 inflammatory markers.
When it comes to women, as noted in a 2020 study, “Berberine is shown to be effective against insulin resistance and obesity, particularly against visceral adipose tissue (VAT). Because of these properties, researchers theorized that berberine could be effective in PCOS treatment…. [B]erberine is safe to use in premenopausal women who want to get pregnant and showed few side effects in all the cited studies. In conclusion, the use of berberine for PCOS is safe and promising, even if more studies are needed to create a consensus about the dosage of berberine useful for long-term therapy.”
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.
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