Effects of Berberine on Metabolism, Lipids, Blood Sugar, and Gut Health
Introduction :Thereberberineis a natural alkaloid derived from various plants (Coptis, Berberis, etc.), traditionally used in Chinese medicine. In recent years, numerous scientific studies – clinical trials, systematic reviews, meta-analyses and preclinical work – have evaluated its potential beneficial effects on metabolism and various metabolic pathologies. We present below a structured summary of these effects, with the doses and durations studied and the main results observed, in four areas:(1)general metabolism (insulin sensitivity, cellular metabolism, energy),(2)fat management (blood lipids, body weight, adipose tissue),(3)blood sugar control (fasting blood sugar, HbA1c, postprandial, diabetes), and(4)intestinal health (microbiota, intestinal barrier, digestive inflammation, gut-brain axis). Key scientific references are provided.
1️⃣ General metabolism: insulin sensitivity, cellular metabolism and energy
- Improved insulin sensitivity
Multiple studies indicate that berberine improves insulin action and reduces insulin resistance. For example, a meta-analysis (2021) of 18 randomized clinical trials concluded that berberine, as a single treatment,significantly decreases the HOMA-IR index(measure of insulin resistance) compared to placebo. In patients with non-alcoholic fatty liver disease (NAFLD), a set of 10 RCTs showed a marked reduction in HOMA-IR (standardized effect size ≈ –1.56,p<0.01) after a few months of berberine – reflecting a notable improvement in insulin sensitivity. Similarly, trials in type 2 diabetes have measured a significant decrease in fasting insulin levels (e.g., about –3 μIU/mL on average) with berberine.
These improvements are typically seen with oral doses of ~1 to 1.5 g per day of berberine for durations of 2 to 4 months, although some studies have used up to ~2 g/day.
Note that a recent dose-response analysis suggests that a dose of approximately1.8 g/daywould optimize the reduction of insulinemia and HOMA-IR.
The duration of treatment also has an impact: certain metabolic parameters continue to improve beyond 3 months, with a meta-analysis indicating, for example, that the effect on fasting blood sugar is maximal around ~40 weeks of treatment.
- AMPK activation and cellular metabolism
Mechanistically, berberine acts as aAMPK activator(AMP-activated protein kinase), a central enzyme regulating cellular energy metabolism. Basic research has shown that berberineactivates AMPK and improves insulin sensitivityin rodent models of insulin resistance. Specifically, berberine causes a slight inhibition ofmitochondrial complex I, which increases the AMP/ATP ratio in the cell and leads to the activation of AMPK – a mode of action similar to that of metformin. Berberine-induced AMPK activation stimulates glucose consumption and fatty acid catabolism (promotingglycolysisand lipid oxidation) while inhibiting hepatic glucose production, thus contributing to better energy balance.
Consistently, AMPK activation by berberine is accompanied by an increase inadiponectin(insulin-sensitizing hormone) and improved insulin signaling in peripheral tissues.
The importance of this AMPK pathway is underlined by the experts' conclusions: mitochondrial complex I appears as amajor targetcompounds that improve metabolism, and berberine – through this action – emerges as a promising therapeutic candidate in type 2 diabetes and metabolic syndromes.
- Energy and energy expenditure:
In addition to improving biochemical parameters, berberine may influence theenergy expenditureof the body. Studies indicate that it could increase thethermogenesisvia the activation of brown adipose tissue (BAT) and thebrowningwhite adipose tissue (conversion of white fat cells to beige type, which is more metabolically active). For example, in obese mice, berberine increases caloric expenditure, improves cold tolerance and stimulates the expression of thermogenesis genes (such as UCP1) in adipose tissue.
These effects result in aincreased fat oxidationand a limitation of lipid storage.
At the same time, a slight increase in basal metabolism (slightly increased body temperature, a sign of increased thermogenesis) is often observed in treated subjects.
All of these observations suggest that berberine, by modifying cellular mitochondrial and hormonal activity,improves energy efficiencymetabolism – that is, it helps the body better use nutrients as a source of energy rather than storing them.
2️⃣ Fat management: blood lipids, body weight and adipose tissue
-Reduction of blood lipids (cholesterol, triglycerides)
Berberine has an effectlipid-loweringdocumented by several clinical trials and comprehensive analyses. A recent systematic review (2022) on cardiovascular risk factors showed that berberine supplementation (typically 1 g/day for 8–24 weeks) results insignificant reductions in triglycerides(–23.7 mg/dL on average), of thetotal cholesterol(–20.6 mg/dL) andLDL cholesterol(~–9.6 mg/dL) compared to placebo (p<0.001 for each).
Simultaneously, aslight increase in HDL cholesterolis observed (+1.37 mg/dL on average,p<0.01). These results confirm the conclusions of previous analyses that berberineimproves lipid profileby reducing atherogenic circulating fats while elevating “good” cholesterol. Proposed mechanisms include increased expression of hepatic LDL receptors (promoting LDL clearance from the blood) and modulation of hepatic AMPK, which reduces lipid synthesis.
Reported effective doses range from 500 mg to 1.5 g twice daily (often 1.0–1.5 g/day total). A dose–response meta-analysis suggests that approximately1 g/dayof berberine is the dose that optimizes reductions in triglycerides and total cholesterol.
Note: In studies, berberine is generally well tolerated hepatically, with no significant elevations in liver enzymes observed compared to placebo.
- Weight loss and reduction of fat mass
Particular interest has focused on the effect of berberine in theobesityand overweight.
The data converge to indicate amodest but significant weight lossunder berberine, particularly at doses ≥1 g/day and for durations >8 weeks.
A meta-analysis of 12 RCTs (2020) found that berberine induces on average−2.07 kgweight compared to the control group (difference in means, 95% CI [–3.09; –1.05],p<0.001).
This weight loss is accompanied by a significant reduction inbody mass index(on average –0.47 kg/m²) andwaist size(approximately –1.1 cm), indicating a decrease in abdominal adipose tissue.
The effects are more pronounced in subjects with metabolic syndrome or NAFLD. For example, in overweight NAFLD patients,4 weeksof berberine (~1.5 g/day in 3 doses) were sufficient to reduce theaverage weight of about 1.2 kg(from 71.2 to 70.0 kg,p=0.011) and thevisceral/subcutaneous fat ratio(from 0.41 to 0.37,p=0.026), compared to the initial situation.
In the long term, studies of 3 months and longer report greater weight losses in some individuals (up to –5 kg), although individual variations are large.
In parallel,systemic inflammationtends to decrease: C-reactive protein (CRP) decreased by an average of –0.42 mg/L under berberine in a meta-analysis, suggesting a reduction in adiposity-related inflammation.
- Effects on adipose tissue (brown and white):
Pioneering work indicates that berberine favorably modifies thebiology of adipose tissue. On the one hand, sheactivates brown adipose tissue (BAT), responsible for thermogenesis: in a study conducted in 10 overweight patients with NAFLD, berberine supplementation for only1 monthresulted in asignificant increase in BAT mass and activity(measured by FDG PET/CT).
An increase in detectable brown fat volume and metabolism (increased maximal SUV and glucose uptake) was noted, correlated with weight loss and improved insulin sensitivity.
On the other hand, berberine promotes the"browning"white adipose tissue (transformation of white adipose cells into more active “beige” adipocytes).
In high-fat fed mice, chronic berberine treatment stimulates the expression of key genes in brown adipogenesis (e.g.,UCP1,PRDM16) and increases the presence ofmultilocular lipid dropletscharacteristics of brown adipocytes in subcutaneous white adipose tissue. This results in an elevation of theenergy expenditurerest and a decrease in pathological lipid storage.
Mechanistically, berberine has been shown toactivates the AMPK–PRDM16 axisin adipocytes, leading to DNA demethylation at the promoter of PRDM16 (a master regulator of brown biogenesis) and thus the conversion of fat cells to the brown/beige phenotype.
Conversely, in genetically modified mice lacking AMPK in adipose tissue, berberine was no longer able to activate thermogenesis, confirming that the effect is mediated by adipocyte AMPK.
In summary,Berberine helps reduce body fat byincreasing fat burning(via the brown fabric) and inreducing storage(via improved insulin sensitivity and browning of white adipose tissue).
These properties explain why it can improve conditions related to excess fat, such as hyperlipidemia and fatty liver.
Moreover, the aforementioned meta-analysis in NAFLD found not only improvements in blood lipids, but alsodecreased liver enzymesALT/AST/GGT – a sign of decreased fat accumulation and inflammation in the liver.
3️⃣ Blood sugar control and anti-diabetic effect
- Decrease in fasting blood sugar and HbA1c
Berberine has notable propertiesantidiabeticsIn people with type 2 diabetes or prediabetes, it significantly lowers blood sugar levels.
A recent global meta-analysis (2023,umbrellarandomized trials) quantified that berberine reduces thefasting blood sugarof approximately –0.77 mmol/L on average (≈ –14 mg/dL) compared to placebo. Similarly, theglycated hemoglobin (HbA1c), an indicator of glycemic control over 3 months, decreases by approximately–0.5 percentage pointsunder berberine (e.g., 7.5% to 7.0%).
These reductions, although modest, are clinically significant and comparable to the efficacy of some first-line oral antidiabetic drugs.
Indeed, a landmark controlled trial showed that 3 months of berberine (500 mg × 3/day) in newly diagnosed diabetic patientsdecrease HbA1c by about 2%(falling on average from 9.5% to 7.5%), an improvementequivalent to that obtained with metforminat the same dosage.
In this same trial, berberine lowered fasting blood glucose from ~10.6 to 6.9 mmol/L, and postprandial blood glucose (2 hours after meal) from ~19.8 to 11.1 mmol/L, results that were superimposable on those of the metformin group.
These data suggest that berberine may control blood sugar almost as well as standard treatment in some patients,particularly in combination with hygiene and dietary measuresIn practice, most clinical studies on blood glucose have used total doses of 1 to 2 g/day (divided into 2–3 doses with meals) for3 months, which seems sufficient to observe a clear reduction in HbA1c. It should be noted that the hypoglycemic effect of berberine often manifests itself gradually (a few weeks), unlike the more rapid action of metformin.
- Improvement of postprandial glycemia and insulin-mimetic action
In addition to fasting blood sugar, berberine helps controlpostprandial blood sugar spikes.
For example, in the trial mentioned above, the ~–8.7 mmol/L drop in blood glucose 2 hours after a meal under berberine illustrates a better metabolism of ingested sugars.
Mechanically, this is explained by several complementary effects: (i)slowing of carbohydrate absorptionat the intestinal level (berberine modestly inhibits certain digestive enzymes and glucose transporters), (ii)stimulation of incretin secretionintestinal (GLP-1) via microbiota changes, which increases post-meal insulin secretion, and (iii)improved glucose uptake by tissuesperipherals through the activation of AMPK and the increase of GLUT4 transporters.
Studies also indicate that berberinelowers hyperinsulinemia: in one review, fasting insulin decreased by about –1 μIU/mL on average (and up to –20 to –30% in some patients), reflecting improved insulin sensitivity. In fact, berberine acts somewhat like a natural “insulin sensitizer”: it does not cause excessive insulin secretions, butoptimizes the body's responseto endogenous insulin. This resulted in a decrease inHOMA-IR indexin many studies of diabetics and obese people. For example, one meta-analysis noted a decrease in HOMA-IR of approximately –0.7 (SMD) with berberine, and the study in NAFLD found a ~23% reduction in HOMA-IR after 1 month of treatment. Overall,the anti-diabetic effects of berberineare similar to those of biguanides: less hepatic glucose production, better muscular use of glucose, and slight inhibition of intestinal alpha-glucosidase.
- Clinical use and safety
Because of these effects, berberine is proposed asadjuvant therapy in type 2 diabetesor metabolic syndrome. It can be used in addition to conventional treatments (metformin, insulin, etc.) – moreover, trials have shown that adding 1 g/day of berberine to metformin treatment improves HbA1c more than with metformin alone (additional reduction ~–0.6%).
Berberine tolerance is generally goodwithout severe side effectsreported to usual doses.
The most common adverse effects are gastrointestinal in nature (≈20–30% of patients may experience transient cramps, diarrhea, or constipation).
These symptoms are usually mild and transient, and can be minimized by starting at a lower dose and gradually increasing. Unlike some antidiabetic drugs, berberine does not cause frank hypoglycemia in non-diabetics because its action depends on the presence of initial hyperglycemia.
Finally, no significant hepatic or renal toxicity was noted at the doses studied over 2–3 months. Thus, berberine appears to be an agentonand potentially useful in improving glycemic control, particularly in patients intolerant to or inadequately controlled by standard medications.
4️⃣ Gut health: microbiota, intestinal barrier, digestive inflammation and gut-brain axis
- Modulation of the intestinal microbiota
A key aspect of berberine is itslow intestinal absorption(modest oral bioavailability), which means that a significant proportion reaches the colon and interacts with the microbiota.
Numerous studies show that berberinemodifies the composition of the intestinal florain a beneficial way.
For example, in animals, treatment with berberine results in aglobal restructuring of the microbiotawith a marked increase in certain beneficial bacteria such asAkkermansia muciniphila(known to strengthen the mucous barrier and improve metabolism). At the same time, there is often an increase in bacteriaproducers of short-chain fatty acids (SCFAs)asButyricimonas,FaecalibacteriumOrRoseburia, and a decrease in pro-inflammatory or pathogenic bacteria (e.g., certainProteobacteria).
These changesincrease butyrate productionand other SCFAs, which have a local anti-inflammatory effect and stimulate GLP-1 secretion, indirectly contributing to the improvement of blood glucose and digestive inflammation. Notably, in a mouse model of diabetes, oral berberine enriched the microbiota with butyrate-producing bacteria, increased fecal butyrate levels, and this was associated with improved glucose tolerance.
Remarkably, it has been shown thatThe metabolic efficiency of berberine depends partly on the microbiota: In mice treated with berberine, eradication of the intestinal flora by antibiotics removes some of the benefits of berberine. This suggests that berberine acts synergistically with the microbiota – possibly by being converted by certain bacteria into active metabolites and by modulating metabolic pathways (e.g., bile acid and tryptophan metabolism).
In summary, berberine is considered a modulator of the intestinal ecosystem,promoting eubiotic flora(balanced) to the detriment of a pro-inflammatory dysbiotic flora.
- Strengthening the intestinal barrier and reducing digestive inflammation
Berberine exerts protective effects on theintestinal mucosaand thepermeability. In models ofcolonic inflammation(experimental colitis), it has shown an ability torestore the intestinal barrierand reduce local inflammation. For example, in rats with DSS (dextran sulfate sodium)-induced colitis, treatment with7 dayswith berberine (40 mg/kg/day) significantly improved symptoms andrepaired the epithelial barrierdamaged.
We observed areduction of ulcerationand intestinal permeability, correlated with changes in the microbiota (increase inBacteroidesAndAkkermansia, beneficial bacteria involved in mucus production and immune regulation).
Berberine also modulates specific metabolic pathways, such astryptophan metabolismbacterial and AhR receptor activation, which contributes to the barrier and anti-inflammatory effect.
In experimental ulcerative colitis, berberineprotects the mucous membraneinrebalancing the microflora(increase in lactobacilli, etc.), instrengthening tight junctionsbetween epithelial cells, and inreducing pro-inflammatory cytokineslocal. Concretely, after a few days of treatment, we observe a marked decrease in inflammation markers (e.g. lessTNF-αin the tissues) and a normalization of colonic architecture. Studies also report a decrease insystemic intestinal permeabilityunder berberine, measured by a decrease in circulating LPS and LPS-binding protein (LBP) – indicating less translocation of bacterial toxins across the intestinal wall.
Thus, berberine helps reduce the phenomenon of "leaky gut" (intestinal hyperpermeability) associated with chronic inflammatory and metabolic diseases. It is worth noting that these digestive anti-inflammatory properties are manifested both in animal models and, in a preliminary way, in humans: for example, a pilot trial in patients with irritable bowel syndrome showed that taking berberine for 8 weeks reduces markers of intestinal inflammation and improves mucosal integrity (measured by the lactulose/mannitol test) compared to placebo.
- Effects in irritable bowel syndrome (IBS) and SIBO
In digestive medicine, berberine has been explored as a therapeutic option in functional disorders such as IBS (irritable bowel syndrome) and SIBO (small intestinal bacterial overgrowth). The results are encouraging especially forDiarrhea-predominant IBS (IBS-D).
Adouble-blind randomized clinical trial(Chenet al., 2015) on IBS-D patients revealed that 4 weeks of berberine (2 × 200 mg/d) significantly reduced thefrequency of diarrheaand theabdominal paincompared to placebo.
Patients taking berberine reported fewer loose stools per day, improved pain scores, and better overall treatment satisfaction. Another real-world clinical study (2019) confirmed these benefits and suggested that a combination of berberine and curcumin may potentiate the effect on bloating and abdominal discomfort.
Mechanistically, berberine is thought to alleviate IBS-D byreducing neurogenic inflammationand thevisceral hypersensitivitystress-induced.
In rats subjected to chronic stress (model of functional colopathy), berberine (200 mg/kg po) hassuppressed visceral hypersensitivityAnddecreased the activation of colonic mast cells and spinal microglia(involved in the perception of intestinal pain).
This effect is partly mediated by the microbiota: berberine enriched the bacteria producing SCFAs with anti-inflammatory properties in these animals, suggesting thatthe microbiota–gut–brain axisis modulated (SCFAs can act on enteric and central neurons). This illustrates how berberine, via microbial modifications, can influence the enteric and even central nervous system.
On a practical level, the use of berberine in gastroenterology should be done with caution: weavoid using it in case of IBS with constipationpredominant, because berberine tends to slow down transit (theconstipationis the most commonly reported GI side effect with berberine).
It is therefore mainly used in diarrheal or mixed forms, and possibly in association with non-absorbed antibiotics (e.g. rifaximin) in SIBO for its moderate local antimicrobial action.
- Gut-brain axis interactions and neuroinflammatory effects
The benefits of berberine's gut modulation are not limited to the digestive tract – they extend beyond it, to thebrain.
Recent findings suggest that berberine may exert effectsneuroprotectors via the gut-brain axis. For example, in a mouse model ofcerebral hemorrhage(hemorrhagic stroke), oral administration of berberine hasattenuated post-stroke neuroinflammationand improved neurological recovery.
This intriguing result was partly attributed to the action of berberine on the intestine: treated mice had a strengthened intestinal barrier (less translocation of bacterial LPS) and an altered microbiota in favor of anti-inflammatory strains. Moreover, when the microbiota was eliminated (antibiotics) or when the microbiota of berberine-treated mice was transplanted into control mice, it was possible to demonstrate thatthe neuroprotective effect depended on the microbiota.
In other words, berberine reduces brain inflammationviagut-derived mediators (possibly by decreasing circulating inflammatory metabolites such as LPS, and increasing beneficial metabolites).
These observations open the way to potential applications of berberine in disorders such asdepressionor neurodegenerative diseases where the gut-microbiota-brain axis plays a role. Moreover, studies in chronically stressed rats have noted an improvement in depressive behaviors with berberine, correlated with a restoration of intestinal eubiosis and an increase in circulating short-chain fatty acids.
Although preliminary, these results suggest that berberine, insimultaneously targeting the gut and inflammation, could have beneficial pleiotropic effects beyond metabolism (e.g., decreased neuroinflammation, improved cognitive function in certain diseases – subject of current research).
5️⃣ Conclusion:
In synthesis, berberine is a natural compound withmultiple beneficial effectsdocumented by modern science.
Sheimproves carbohydrate metabolism(lower blood sugar, HbA1c, better insulin sensitivity) andlipid(reduction of triglycerides, LDL cholesterol, aid in moderate weight loss), through mechanisms involving AMPK activation and hormonal modulation.
It also exerts an actionanti-adiposityby stimulating fat burning (activation of brown tissue, browning of white tissue) and reducing harmful lipid deposits.
Furthermore, berberinetargets the intestinal ecosystem: it rebalances the microbiota, strengthens the intestinal barrier and reduces digestive inflammation – effects which indirectly contribute to its metabolic benefits and which establish it as a link between the intestine and other organs (liver, adipose tissue, brain).
Clinical studies, including several randomized trials and meta-analyses, confirm these results in humans for doses typically between 0.9 and 1.5 g per day for 2 to 3 months (with dose-dependent efficacy up to ~2 g/d).
Tolerance is generally good, apart from transient digestive problems in a minority of subjects.
Although berberine does not replace established medical treatments, itstands out as a promising adjuvantin the management of type 2 diabetes, dyslipidemia, metabolic syndrome, and possibly certain intestinal inflammatory or neurological diseases associated with the microbiota. Further research, particularly over the longer term and in other populations, is underway to better define its therapeutic potential and detailed mechanisms of action.
Main references:Yeet al., 2021 (Front. Pharmacol.); Asbaghiet al., 2020 (Clin Nutr ESPEN); Weiet al., 2022 (Front. Nutr.); Nazariet al., 2024 (Clin. Ther.); Guoet al., 2023 (J. Transl. Med.); Wuet al., 2019 (Cell Death Dis.); Turneret al., 2008 (Diabetes); Zhanget al., 2008 (Metabolism) – trial vs metformin; Chenet al., 2015 (Phytother. Res.) – IBS-D trial; Liuet al., 2023 (Aging),etc.(see quotes in the text).
