The increasing popularity of semaglutide (Ozempic and Wegovy) for weight loss has sparked interest in alternative options like berberine. Berberine, a natural compound with a long history in traditional medicine, is now being investigated for its potential role in weight management. This article aims to provide a comprehensive overview of berberine, its mechanisms of action, and the existing evidence regarding its effects on weight loss.
What is Berberine?
Berberine is a naturally occurring isoquinoline alkaloid found in various plants, including Coptis chinensis (Huang Lian), Berberis aristata, and others used in traditional medicine systems like Ayurveda and Traditional Chinese Medicine (TCM).
Plants containing berberine have a long history of use in both Ayurvedic and Chinese medicine. In modern times, plants containing berberine have been used for infections, skin diseases, digestive disorders, and other conditions. Berberine is currently being studied for its effects on diabetes and risk factors for heart disease. Recently, it has become popular as a potential weight loss aid.
In TCM, it has been used for over 2,000 years to address diabetes and gastrointestinal issues, especially diarrhea.
How Does Berberine Work?
Berberine exhibits a range of pharmacological activities that may contribute to its potential weight loss effects. Key mechanisms include:
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Impact on Gut Microbiota
In preclinical models, berberine demonstrates that it affects gut microbiota by reducing diversity of microbes starting at a dosage of 100 mg/kg/day. Berberine can modulate the diversity of gut microbes at the dose of 500 mg/day.
Glucose Regulation
In animal models, Berberine explicates an action on glucose through the inhibition of α-glycosidase at a dose of 200 mh/kg/day. In addition, Berberine is found to have a beneficial impact on gene regulation for the absorption of cholesterol at a daily dose of 300 mg in humans, an amelioration on glucose accumulation at 1.0 g daily dose was also observed. Berberine helps regulate glucose levels by improving how your cells respond to insulin and slowing down the breakdown of carbohydrates in the gut. On average, berberine may lower blood sugar by about 0.5 to 0.7%.
Adipocyte Differentiation
Berberine is also known to be effective against differentiation of adipocytes through a decrease in LXRs, PPARs, and SREBPs expression at 150 mg/kg/day.
Hepatic Gluconeogenesis
Other mechanism ascribed to Berberine are related to its inhibition of hepatic gluconeogenesis through the Phospheoenolpyruvate carboxykinase (PEPCK), Glucose-6-phosphate (G6Pase) and AMP-activated protein kinase (AMPK). Its metabolic effects, particularly its ability to activate AMPK, can help the body burn fat more efficiently. Berberine, on the other hand, activates AMPK which is an enzyme that influences metabolism and energy use.
Lipid Levels
Furthermore, Berberine (associated to Red Yeast Rice) is effective in decreasing lipid levels in rats, which consequently lowers the change of weight gain at dosage of 40 mg/kg to 380 mg/kg/day. Berberine may help lower LDL “bad” cholesterol and triglycerides, but it’s important to understand that the reductions are mild compared to what you’d get from statins.
Read also: Does Berberine Help with Weight Loss?
Berberine and Obesity: Preclinical and Clinical Evidence
Preclinical Studies
Preclinical studies on berberine have demonstrated promising results in various models:
Weight Gain Attenuation: Berberine administration (150 mg/kg/day) effectively reduced body weight gain in high-fat diet (HFD)-induced obese rats without affecting caloric intake.
Food Intake and Adiposity Reduction: Parenteral berberine administration (10 mg/kg daily for 3 weeks) in HFD-fed murine models significantly reduced food intake, body weight, adiposity indices, leptin concentrations, and glycemic parameters.
Vascular Modulation: Berberine (200 mg/kg) normalized abnormal nitric oxide (NO) overproduction and diminished noradrenaline (NA) synthesis in perivascular adipose tissue (PVAT) of obese rats, demonstrating its vascular modulatory capacity.
Lipid-Lowering Efficacy: Berberine (200 mg/kg oral dose) in hyperlipidemic mice modulated gut microbiota, enhancing Blautia producta populations, which subsequently upregulated hepatic low-density lipoprotein (LDL) receptor expression and promoted cholesterol clearance.
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Dose-Dependent Effects: Oral supplementation (100-200 mg/kg/day) mitigated HFD-induced weight gain. Both low-dose (150 mg/kg/day) and high-dose (300 mg/kg/day) regimens over 4 weeks achieved comparable weight reduction in obese mice, independent of appetite modulation.
Insulin Sensitivity and Adiposity: Berberine administration (100 mg/kg/day) demonstrated marked therapeutic efficacy in HFD-induced murine models, mitigating insulin sensitivity impairment, reducing total body mass and adipose tissue proportion, and normalizing serum metabolic markers.
Glucocorticoid-Induced Lipodystrophy: Berberine (100, 200, and 500 mg/kg) ameliorated glucocorticoid-induced lipodystrophy in a dose-dependent manner.
Muscular Strength and Neuromuscular Performance: Chronic oral berberine administration (100 mg/kg in saline) over 8 weeks significantly enhanced muscular strength and neuromuscular performance in rodent models, mitigating body mass accumulation and ectopic lipid deposition, and alleviating obesity-associated dyslipidemia.
Hepatic Lipid Accumulation: Berberine modulated perilipin family protein expression involved in lipid droplet (LD) metabolism, reducing LD diameter in hepatocytes.
Clinical Trials
Clinical trials have also investigated the effects of berberine on weight loss and related parameters:
Lipid Profile Improvement: Daily supplementation with 1.5 g berberine elicited marked reductions in serum lipid profiles among obese participants, achieving 23% and 12.2% decreases in triglyceride (TG) and total cholesterol (TC) concentrations, respectively.
Adiposity Reduction: Thrice-daily preprandially administration of 500 mg berberine resulted in statistically significant reductions in adiposity indices, including BMI, visceral fat proportion, and overall adipocyte volume.
Population-Specific Benefits: In cohorts with obesity and prediabetes, 12-week berberine interventions (1.5 g/day) produced clinically relevant decreases in waist circumference and BMI.
Trunk Fat and Hepatic Lipid Accumulation: Berberine administration (1500 mg/day) over 3 months attenuated trunk fat mass and hepatic lipid accumulation, liver fibrosis and steatosis severity.
Meta-Analysis Confirmation: A meta-analysis of six randomized clinical trials (RCTs; n = 501) quantitatively confirmed berberine’s therapeutic potential, establishing 1000 mg/day as an effective dosage for improving lipid parameters, insulin sensitivity, hepatic function markers, and steatosis progression.
A 2022 review of 18 studies that examined the effect of berberine on body weight and 23 that examined its effect on body mass index (BMI; a value based on weight and height that may help determine whether a person has a healthy weight) found significant decreases in both weight and BMI in people who took berberine. Effects on weight were seen primarily in people who took berberine in doses of more than 1 gram per day and for more than 8 weeks. Many of the studies included in this review had a high risk of bias, and the outcomes of individual studies were inconsistent. Therefore, additional, high-quality research would be needed to allow definite conclusions to be reached about whether berberine reduces weight and BMI. Assessing the effects of berberine is also difficult because the amounts and formulations of berberine used in different studies have varied widely, and most of the study participants had health problems, such as diabetes or fatty liver disease, that might have influenced the results. In addition, most studies that looked at the effects of berberine on weight and cardiovascular risk factors were conducted in Asian countries; very few were done in North America.
Berberine vs. Other Weight Loss Medications
While berberine shows promise, it is crucial to compare it to established weight loss medications:
Berberine vs. GLP-1 Agonists (e.g., Semaglutide)
Berberine is often compared to metformin as they have similar side effects, mainly digestive issues like nausea, cramping and diarrhea, and most people experience side effects in the same way. Metformin is one of the most widely prescribed medications for Type 2 diabetes and costs less than berberine supplements.
- Efficacy: GLP-1 medications have stronger research backing and work by mimicking a hormone that regulates appetite and blood sugar. While berberine may support modest weight loss, it doesn’t mimic the hormone GLP-1 or produce the same appetite-suppressing effects.
Berberine vs. Metformin
- Mechanism: Berberine activates AMPK, influencing metabolism and energy use, while metformin is a widely prescribed medication for Type 2 diabetes that also affects glucose metabolism.
- Side Effects: Both berberine and metformin can cause digestive issues like nausea, cramping, and diarrhea.
Dosage and Safety
Most studies suggest a dosage of 500 milligrams up to three times per day, but starting on the lower end and gradually increasing it is the most recommended approach. Berberine is typically taken before or between meals, rather than with food.
Having served as an over-the-counter gastrointestinal agent in Chinese pharmacopeia for seven decades, BBR demonstrates exceptional tolerability in clinical applications, particularly for diarrhea management.
Berberine is considered safe and well tolerated for most adults when used as directed. Some side effects of berberine have been reported in research studies, primarily gastrointestinal symptoms such as nausea, abdominal pain, bloating, constipation, or diarrhea. Notably, co-administration strategies have emerged to mitigate these effects. Cui et al. identified quercetin (QR), a bioactive constituent of Amomum villosum Lour. (AVL), as an effective adjuvant for alleviating BBR-induced constipation through synergistic pharmacological interactions.
Precautions:
- Medication Interactions: Berberine can interact with certain medications, particularly those for diabetes and blood pressure. It's important to know that berberine can alter how quickly the liver breaks down medications - including anti-clotting drugs and immunosuppressants - and change their effectiveness.
- Infants: Exposure to berberine has been linked to a harmful buildup of bilirubin in infants, which can cause brain damage. Therefore, berberine is likely to be unsafe for infants.
- Pregnancy and Breastfeeding: Berberine may also be unsafe for use during pregnancy or while breastfeeding because of possible effects on the fetus or infant.
Challenges and Future Directions
Despite its potential, berberine faces challenges:
Bioavailability
Its clinical utility is hindered by poor oral bioavailability (< 1%) in rodent models pharmacokinetic studies due to intestinal efflux, hepatic metabolism, and physicochemical instability.
Regulation
Berberine is sold as a dietary supplement in the United States, and the Food and Drug Administration (FDA) “does NOT have the authority to approve dietary supplements for safety and effectiveness.” As with all dietary supplements, it’s impossible to know for sure whether the ingredients listed on the bottle accurately represent what’s inside the bottle. Since the FDA doesn't regulate dietary supplements, there's no guarantee how much berberine is contained in a product.
Research Limitations
Many of the studies included in this review had a high risk of bias, and the outcomes of individual studies were inconsistent. Therefore, additional, high-quality research would be needed to allow definite conclusions to be reached about whether berberine reduces weight and BMI. Assessing the effects of berberine is also difficult because the amounts and formulations of berberine used in different studies have varied widely, and most of the study participants had health problems, such as diabetes or fatty liver disease, that might have influenced the results. In addition, most studies that looked at the effects of berberine on weight and cardiovascular risk factors were conducted in Asian countries; very few were done in North America.
Future research should focus on:
- Improving berberine's bioavailability through novel formulations.
- Conducting large-scale, randomized, multi-center clinical trials.
- Investigating the long-term effects of berberine on weight management and metabolic health.