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Berberine is an alkaloid extracted from plants with a history of usage in traditional Chinese medicine. It is most commonly used as a supplement for its anti-inflammatory and anti-diabetes properties, and is also used to reduce liver production of glucose.
We recommend that one 500 mg capsule of Berberine be taken between two to four times per day. It is strongly recommended that each capsule of Berberine taken per day be consumed at least 3 hours after the last one, as taking too much at once can increase the likelihood of gastrointestinal side effects.
Berberine should be taken along with or directly after a meal in order to maximize its beneficial effect on blood glucose levels.
When taken at normal doses Berberine is non-toxic and is usually well tolerated. The most common side effects reported are stomach upset, cramping, and diarrhea. These side effects are more likely to occur if more than 1 capsule is taken at a time.
Berberine should not be combined with any prescription medications without first consulting a physician as serious adverse reactions can occur when it is combined with certain drugs, specifically Phosphodiesterase inhibitors and microlide antibiotics.
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Berberine is a bright yellow alkaloid extracted from numerous plants that has been used in traditional Chinese and Ayurvedic medicine. Most commonly found in Indian Barberry, Oregon Grape, Pellondendron amurense, Goldenseal, and Chinese goldthread, Berberine was traditionally used to combat gastrointestinal issues and to support overall health. (1,2,3)
More light has been shed on berberine in recent years, as over a third of 2,800 studies have been published in the last five years. (3) Prior to that, most of the knowledge on berberine was originally based on a 1997 article published in Alternative Medicine Review. While berberine had been known for its traditional uses, this article by Tim Birdsall and Greg Kelly was the first to focus on berberine for antimicrobial and anti-inflammatory uses. (3)
As a dietary supplement, berberine has shown to have positive effects on blood sugar and cholesterol. It works to reduce insulin resistance and can activate the enzyme, Adenosine Monophosphate-Activated Protein Kinase (AMPK). (4) AMPK acts as the body’s central regulator for cell energy and metabolism.
Through AMPK activation, berberine’s primary benefits are its ability to regulate blood sugar and cholesterol levels. (9,10,11,12)
Regulates Blood Sugar:
AMPK acts as a metabolic master switch that decreases insulin resistance and increases the expression of insulin receptors. Berberine has the added effects of regulating blood glucose levels:
Berberine, and to a lesser extent its metabolites, have shown to decrease LDL, “bad cholesterol” (13,20) By increasing activity of the LDL receptor in the liver via the JNK pathway. (20)
Berberine aids in decreasing LDL levels in blood by regulating LDL receptors (22,23):
When a mutated HNF1A binds with PCKS9, it inhibits the ability of PCSK9 to control LDL receptors. Berberine acts by inhibiting HNF1A to allow PCKS9 to break down LDL receptors before they reach the cell surface. (22,23)
Via AMPK activation, berberine also inhibits lipid synthesis in hepatocytes, the cell that makes up 70 – 85% of the liver’s mass. (24)
Other than glucose and cholesterol regulation, berberine has shown other benefits that will be discussed further in the “Berberine Research” section that include:
Berberine is most commonly found as a powdered capsule for supplementation. Berberine should be taken with a meal or shortly before a meal for two reasons. Firstly, there is a blood glucose and lipid spike that comes with eating and berberine can help to combat this. Secondly, the absorption of berberine has previously been questioned, and when taken with food it has shown to absorb more effectively. More recently however, berberine has shown to be well absorbed, but quickly metabolized. (3)
As berberine has a short half-life, it is best to supplement several times over the course of a day rather than take the full dosage at one time.
Berberine Dosage Instructions
The recommended dosage for berberine is between 900mg to 1,500mg per day. The most common recommendation is a 500mg dose with meals, three times a day. Dosages should be spaced at least three hours apart to decrease the risk of side effects.
Half-Life and Duration of Effects
Berberine has a relatively short half-life of approximately 3 hours. Because of this, consistent supplementation of 500mg, three time a day, is recommended.
Berberine has been reported to be very safe and well tolerated. If you’re taking any other supplement or medication to control blood sugar, consult with a physician prior to supplementing with berberine to ensure blood sugar remains in the proper range.
Repeated use of berberine has shown to inhibit cytochromes P450. (30) Cytochrome P450 contains the enzymes CYP3A4, CYP2D6, and 2C9. These enzymes are primarily expressed in the liver and are involved in the metabolism of certain drugs and dietary supplements. If you’re currently taking any other drugs or dietary supplements, you should check potential drug interactions as you may need to take lower doses to avoid potentially dangerous effects.
The most commonly reported side effects with berberine are upset stomach, nausea, cramping, or diarrhea. Side effects are more likely to occur if taking more than 500mg per dose. Berberine may lower blood pressure so if you’re currently dealing with low blood pressure, consult with a physician prior to supplementing with berberine.
The primary mechanism of berberine is to activate AMPK. (3,4) AMPK induces several other mechanisms that are involved in biological activities throughout the body. AMPK aids to regulate and normalize lipid, glucose, and energy imbalances. Without AMPK regulating catabolic pathways, there can be an imbalance in blood sugar, lipid abnormalities, and energy. (9) An activation of AMPK has been proposed to reduce the need for various medications, as controlling AMPK can control different health issues. (10)
Triggering AMPK activation increases glycolysis, the breakdown of glucose by enzymes. (11) Glycolysis leads to decreased insulin resistance and decreased oxygen respiration. Berberine also increases the expression of insulin receptors and reduces insulin resistance. (12) Combined with the glycolysis, this helps to explain berberine’s ability to improve glucose control. (11)
Berberine acts to reduce cholesterol through a mechanism that is unique from statins. (13) Berberine upregulates lipoprotein receptor (LDLR) expression independent of element binding proteins. By elevating LDLR expression through a post-transcriptional mechanism, berberine is able to stabilize mRNA. Using an oxidative enzyme as a reporter, there was an identification of a proximal section of LDLR mRNA 3’ untranslated region that was responsible for the regulatory effect of berberine. (13)
AMPK regulation may play a role in cardiovascular health. A reduction in AMPK phosphorylation has shown to protect from arrythmia and reduce infarct size. (14)
Berberine can be metabolized into four different metabolites; Berberrubine, Thalifendine, Jatrorrhizine, and Demethyleneberberine. (7,8) While Berberrubine has shown to be the most potent activator of AMPK and LDL receptors upregulation, all four metabolites work on similar mechanisms of berberine but with reduced potency. (7,8)
Outside of mechanisms relating to AMPK activation, berberine has shown to inhibit acetylcholinesterase (ACHe) activity. (10) ACHe is and enzyme responsible for breaking down acetylcholine. Inhibiting ACHe aids to prevent the breakdown of acetylcholine, the neurotransmitter responsible for memory and learning. During this process, glucagon-like peptide (GLP-1) also increases. (10) GLP-1 is an amino acid long peptide hormone that enhances synaptic plasticity and reduces the aggregation of amyloid β protein, preventing the build-up of amyloid plaques in the brain.
Regulates Blood Sugar (29)
36 individuals with high blood sugar were randomly assigned berberine at 500mg, three times daily. The individuals who were assigned berberine saw significant decreases in hemoglobin A1C, fasting blood glucose, post-meal blood glucose, and plasma triglycerides. A separate study on 48 volunteers saw similar effects in fasting and post-meal blood glucose levels. Additionally, the second study saw a decrease in fasting plasma insulin.
Improves Cholesterol (20)
A group of 40 subjects with moderately high cholesterol levels were administered berberine for 4 weeks. Total cholesterol, LDL, HDL, and triglycerides were all measured prior to and at the conclusion of treatment.
At the conclusion of the study, there were improvements in:
This suggests that berberine can be beneficial for improving cholesterol levels.
Anti-Inflammatory Properties (25)
Berberine been used in traditional Chinese medicines for its anti-inflammatory abilities. To study this, a group of mice had their nose inflamed via dust to mimic rhinitis. The mice were then split into groups and either treated with berberine or not treated.
The group of mice administered berberine so improvements in symptom and allergen serum scores. Additionally, there were improvements in GATA-3 and T-bet levels which are associated with inflammatory responses due to allergies.
May Improve Memory and Learning (26)
A study on rats was conducted to determine the effectiveness of berberine against memory impairment. The rats were split into a control group and a group that received 25 – 100mg/kg of berberine twice daily for 30 consecutive days. The rat’s memory was tested via a Morris water maze paradigm.
Choline esterase (ChE) was used a marker for cholinergic function and was significantly increased in the rats administered berberine. Lipid peroxidation and glutathione levels were markers for oxidative stress and significantly decreased during testing. The increase in ChE and decrease in oxidative stress lead to improvements in cognitive performance, memory, and learning.
Antioxidant in the Liver (27)
Rats were introduced to varying hepatotoxic factors and then split into a control group and berberine administration groups. Berberine, at doses of 50mg/kg, 100mg/kg, or 200mg/kg was administered daily for four weeks. The biomarkers used were alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and hepatic activity of superoxide dismutase (SOD).
Berberine administration lead to a decrease in serum levels of ALT and AST while the activity of SOD was significantly increased. This demonstrates the abilities of berberine to improve liver health through the regulation of the antioxidant system.
Promotes Feelings of Well-Being (28)
A study was conduced on rats to determine the antidepressant-like effect that had been reported with berberine use. Administration of berberine at 5mg/kg saw significant increases in serotonin (between 19-47%) and dopamine (between 31-52%). As serotonin is responsible for feelings of well-being and happiness, and dopamine for motivation, this is thought to be the mechanism behind the antidepressant-like feelings.
Can you use Berberine indefinitely?
Berberine is best to be used in a 6 to 8-week cycle followed by a break.
Is berberine good for the liver?
Berberine has shown to have antioxidant properties for the liver. However, berberine inhibits cytochromes P450 in the liver which may cause drug interactions.
Is berberine a blood thinner?
Although it is not intended to be a blood thinner, berberine has been shown to lower blood pressure. If you’re currently taking any medication to reduce blood pressure you should consult with a physician prior to berberine supplementation.
Does berberine kill parasites?
There is currently a lack of clinical trial evidence to support the theory that berberine can kill intestinal parasites.
Can berberine be taken with probiotics?
Berberine may kill certain probiotic strains and reduce the efficacy of the probiotic supplements.
Is berberine in Turmeric?
Due to their similar colors and anti-inflammatory properties, some people do confuse the two supplements. However, the two are unrelated.
* These reviews are the experiences of the individual customers that submitted them, results may differ from person to person.
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