BERBERINE

A naturally occuring compound in several plant species including barberry, goldenseal and more. Berberine effectively reduces insulin resistance in the level of prescription drugs like metformin, but unlike metformin has never been shown to have negative effects in cancer outcomes. It is certainly the case that reducing insulin resistance has a protective effect in terms of cancer risk, whilst research studies to support that rely on users of metformin. Other reports have successfully combined berberine with metformin and statins to increase impacts. And with other supplements such as red yeast rice too in metabolic disorders , including branded supplments such as Berberol K. (see References)

Insulin resistance leads to elevated blood glucose levels, frequently shown to increase the incidence and spread of tumors. Studies demonstrate its negative impacts in several cancers. Most prominently colorectal, liver, lung, pancreatic, head and neck, and postmenopausal breast cancers. And probable links with gastric, clear cell kidney. Though evidence is mixed for prostate cancer, and non-existent for melanoma, glioma, lymphoma.

Its anti-bacterial actions and support of a health micro-biome contribute to results in some trials showing protection benefits during radiotherapy. There is evidence in clinical trials that berberine reduces recurrence of benign colorectal polyps following surgery, from around a half to around a third of patients. And a trial on berberine chloride to reduce incidence of colorectal cancer in patients having ulcerative colitis. One action proposed is the reduction in a cancer driving bacteria in the gut veillonella parvula

A small trial showed protective effects during radiotherapy. Additionally, berberine has shown strong anti-inflammatory actions inluding reductions of c-reactive proteins and IL-6. And, int the moderation of lipid metabolism, so called fatty acids. Even in reduction of hormone growth factors including leptin. All of these are separately associated with increased progression in various cancers, and all may benefit from reducted activity in the presence of berberine. Effects can take a week or two to materialize.

There are a lot of pre-clinical reports of anti-metastatic effects, though these need more evidence from cancer trials. Whilst absorption is limited, the reality shows its enough and any good quality brand will drive these effects.

TYPICAL ABSORPTION LEVELS

1-5%

EXAMPLES OF IMPROVED OUTCOMES

PENDING

PRE-DIAGNOSIS OR PREVENTION

PENDING

Highlighted Studies

Breast cancer incidence and outcome is strictly related to metabolic disorders…Thus, managing these emerging risk factors, should be a new and optimal strategy in breast cancer prevention and therapy. The authoritative and abundant data present in the literature have pushed important Italian and European societies on cardiovascular and diabetic diseases, to insert BBR in their joint position statement and guidelines in order to accept and advise the use of BBR in selected pati...

Link

Berberine improves insulin sensitivity by increasing the expression and enhancing the activation of insulin receptor….The HOMA-IR index serves as a pivotal parameter for assessing insulin sensitivity. Besides, HOMA-IR enables the quantification of insulin resistance and β cell function based on basal glucose and insulin concentrations, making it a widely utilized surrogate marker for assessing insulin resistance in research studies. In this meta-analysis, the administration of berberin...

Link

Overall, the use of berberine in patients appeared to significantly decrease several inflammatory markers…52 studies were included.  Pooled estimates showed that the use of berberine could significantly reduce the concentration level of C-reactive protein (CRP) [standardized mean difference (SMD= − 1.54) [meaning significant reduction in the majority of cases], tumor necrosis factor-α [SMD = − 1.02], and interleukin 6 (IL-6) [SMD = − 1.17] among patients with Met...

Link

…berberine alone can reduce TG [blood sugars], TC [total cholesterols], LDL, HDL, FPG, and HOMA-IR levels in patients… This meta-analysis on the efficacy and safety of berberine for several metabolic disorders leads to the propel guidelines of berberine in clinical practice… berberine has the potential to treat metabolic disorders such as type 2 diabetes complicated with hyperlipidemia. Compared with traditional statins and metformin, berberine also has great benefits in imp...

Link
BACK TO INDEX

TABLE OF REFERENCES

Help grow the evidence. Login and use the form, or try Feedback and Ideas below.

URLRatingHighlightHighlight 2Visuals (click)
https://ar.iiarjournals.org/content/38/8/4393#Meta-analysis3A natural compound like BBR, has abundantly shown in mono and in add-on therapy profiles, its ability to modulate these pathways without limiting side-effects and could be a safe and valid alternative to conventional drugs in breast cancer prevention and therapy. The authoritative and abundant data present in the literature have pushed important Italian and European societies on cardiovascular and diabetic diseases, to insert BBR in their joint position statement and guidelines in order to accept and advise the use of BBR in selected patients... We suggest it is time to consider this approach in cancer and in a breast cancer setting too.Compared with their nondiabetic counterparts, patients with breast cancer and pre-existing diabetes and in general with metabolic disorders involving dislypidemic conditions too, have a greater risk of cancer incidence and death and tend to present at later stages of disease. Thus, we investigated the pathophysiologic interactions between metabolic disorders and breast cancer and determine whether improvements in their care can be beneficial.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10908013/Meta-analysis3The levels of HOMA-IR were meticulously monitored in a total of 472 patients diagnosed with NAFLD across 5 rigorously conducted RCTs.. The meta-analysis findings support the conclusion that berberine exhibited a potential for reducing HOMA-IR levels (SMD = − 1.56). In the subgroup analysis of NAFLD with diabetes, heterogeneity was effectively reduced to 67%, with no significant reduction observed in the other three subgroup analysesThe HOMA-IR index serves as a pivotal parameter for assessing insulin sensitivity. Besides, HOMA-IR enables the quantification of insulin resistance and β cell function based on basal glucose and insulin concentrations, making it a widely utilized surrogate marker for assessing insulin resistance in research studies. In this meta-analysis, the administration of berberine resulted in a significant reduction in HOMA-IR among patients with NAFLD, as well as those presenting with concomitant diabetes
https://pmc.ncbi.nlm.nih.gov/articles/PMC9135894/Meta-analysis3Despite the limitations of meta-analysis, the robust methodology followed in selecting RCTs for inclusion and in completing the evaluation does facilitate the conclusion that berberine use in patients with MetS and related disorders appears to have significantly decreased inflammatory markers, including CRP, TNF-α, and IL-6. This study provides new and useful evidence for supporting clinical medication decisions for MetS and related disorders and encourages undertaking further RCTs52 studies were included, and the related trials involved 4616 patients. Pooled estimates showed that the use of berberine could significantly reduce the concentration level of C-reactive protein...Overall, the use of berberine in patients with MetS and related disorders appeared to significantly decrease several inflammatory markers
https://pmc.ncbi.nlm.nih.gov/articles/PMC8107691/Meta-analysis3The findings of the present meta-analysis demonstrated that berberine alone can reduce TG, TC, LDL, HDL, FPG, and HOMA-IR levels in patients with metabolic disorders, and this effect was observed in healthy participants. This meta-analysis on the efficacy and safety of berberine for several metabolic disorders leads to the propel guidelines of berberine in clinical practice. These effects indicate that berberine has the potential to treat metabolic disorders such as type 2 diabetes complicated with hyperlipidemia. Compared with traditional statins and metformin, berberine also has great benefits in improving mild cognitive impairment, effectively preventing secondary or the occurrence of drug-induced metabolic encephalopathy...the efficacy of berberine treatment on HOMA-IR. It is reported with 261 volunteers in the control group and 278 in the trial group using a randomized model. After standardization, the HOMA-IR concentration of the trial group decreased by 1.25 (95%CI: 0.25, 2.24) compared with the control group. The I 2 value was 96%, and the p-value was 0.01. The chart illustrates that berberine can reduce the HOMA-IR level of the patients
https://journals.lww.com/cmj/fulltext/2023/11200/berberine_might_block_colorectal_carcinogenesis_by.9.aspxHuman study3The abundance of fecal Veillonella parvula (V. parvula) decreased significantly after BBR administration (P = 0.0016) and increased through the development from CRA to CRC. Patients with CRC with a higher V. parvula abundance had worse tumor staging and a higher lymph node metastasis rate. The intestinal immune pathway of Immunoglobulin A production was activated, and the expression of TNFSF13B (Tumor necrosis factor superfamily 13b, encoding B lymphocyte stimulator [BLyS]), the representative gene of this pathway, and the genes encoding its receptors (interleukin-10 and transforming growth factor beta) were significantly upregulated. Animal experiments revealed that V. parvula promoted colorectal carcinogenesis and increased BLyS levels, while BBR reversed this effect.As one of the important antigens in the intestine, the gut microbiota maintains normal immune tolerance in the intestine,[23] stimulates the maturation of intestinal B cells, participates in constructing intestinal immune defense, and maintains intestinal homeostasis.[24] In the present study, mRNA sequencing of surgical CRC tissue revealed that V. parvula might exert protumor effects through the intestinal immune network for IgA production. The representative gene of this pathway, TNFSF13B, the encoding BLyS and the genes encoding its receptors, is mainly expressed by B cells, and BLyS levels are associated with the function of B cells. Some intestinal B-cell subtypes are linked to poor prognosis in patients with malignancies
https://bmccomplementmedtherapies.biomedcentral.com/articles/10.1186/s12906-019-2715-1Human study3The BV juice intervention over 8 weeks was accompanied by acceptable efficacy and decreased plasma IGF-1, and IGF-1/IGFBP-1 ratio partly could be assigned to enhanced IGFBP-1 level in women with BBD. The intervention caused reductions in the expression levels of PPAR, VEGF, and HIF which are remarkable genomic changes to potentially prevent breast tumorigenesis.This interventional study showed the effectiveness of BV juice supplementation on changes in IGF and IGF-bioavailability in women with BBD. Our findings showed that BV administration resulted in enhanced IGFBP-1 level and reduced IGF-1/IGFBP-1 ratio which both suggest that BV juice might potentially reduce IGF-dependent tumor progression toward malignancy from benign breast disease. In addition, BV juice intervention led to reduction in percent changes of PPAR-γ, VEGF and HIF expressions, highlighting the possible inhibitory effects of BV juice on malignant transformation
https://onlinelibrary.wiley.com/doi/10.1111/ajco.13941Meta-analysis3BBR as an antitumoral phytochemical agent has crucial roles in the suppression of different cancers. The efficacy of BBR in treating GI cancers along with its safety and low cost has attracted the attention of many investigators and clinicians around the world. In this paper, we reviewed the latest evidence evaluating the efficacy of BBR against GI cancers, addressing its mechanistic modes of action. Strong evidence favors powerful anti-proliferative and antitumoral activities of BBR in the management of GI cancers. In one study, the anticancer activity of BBR was investigated in order to evaluate the reduction of the effects of radiation therapy in patients with cervical cancer and lymphoma.177 BBR protected lung cells from damage caused by ionizing radiation in non-small cell lung cancer patients receiving radiation therapy. It selectively sensitized tumor cells to ionizing radiation in glioma patients, whereas healthy cells remained at the same level of sensitivity. BBR's ability to increase chemical sensitivity and reduce the side effects of chemical sensitizers has also been emphasized
https://pmc.ncbi.nlm.nih.gov/articles/PMC3310165/Human study3However, our result is in agreement with the findings from previous large sample, well-designed clinical studies [23, 34], indicating that berberine improves glucose and lipid metabolism disorders. More particularly, we find that berberine can improve insulin sensitivity by adjusting adipokine secretion both in primarily cultured preadipocytes as well as in metabolic syndrome patients, and this was not well characterized in previous human studies.We have confirmed that berberine reduces HOMA-IR and the ratio of leptin and adiponectin. As it inhibits PPARγ2 mRNA expression and has more effects on weight loss and reducing leptin levels, berberine regulates insulin sensitivity with a mechanism different from the insulin sensitizer, thiazolidinediones. Thus, berberine provides an additional way for clinical treatment of metabolic syndrome and obesity-related diseases.
https://pmc.ncbi.nlm.nih.gov/articles/PMC8890747/Human study3Metformin, the classical drug used in PCOS, improves all the parameters in polycystic ovary syndrome women. Berberine may have greater potential to reduce the risk of cardiovascular disease than metformin in PCOS patients due to its effect on body composition, lipid profile, and improvement in hormone status. Myoinositol administration improves endocrine parameters and insulin sensitivity. It may be considered as a first-line option in PCOS patients with insulin resistance without prediabetes or diabetes. It has also been concluded by a meta-analysis that berberine in combination with OCPs is superior to OCPs alone [5]. The present study showed that berberine had an almost similar effect on various parameters as metformin and myoinositol, with the exception of some parameters like WC, WHR, SHBG, FAI, and lipid profile, where it showed significant improvement over other groups (Table 3). Wei et al. also showed significant improvement in WC, WHR, SHBG, and lipid profile with berberine when compared to metformin.
https://www.tandfonline.com/doi/full/10.2147/CPAA.S120032Human study2.5The results of the analysis indicated that the lifestyle intervention has poor efficacy but confirmed the cholesterol-lowering action of lovastatin and its ability to enhance CPK values. Also the analysis confirmed that food supplements containing proper doses of either berberine and silymarin or berberine and RYR significantly improved the lipid profile of patients. In light of the modest CPK increase observed, our results also suggested the possible safety of add-on therapy with food supplements containing low doses of RYR in statin-intolerant subjects. Our finding is likely due to the low content (10 mg/dose/day) of monacolins administeredGlycated hemoglobin and homeostatic model assessment of insulin resistance values were significantly lower (by approximately 9% and 15%, respectively) in the two groups treated with BSM, likely due to the berberine content of the tablets. Lovastatin significantly reduced TC, LDL, and TG by approximately 21%, 26%, and 8%, respectively, while BSM significantly reduced TC, LDL, and TG by approximately 25%, 31%, and 19%, respectively. In statin-intolerant subjects, BSM significantly reduced TC, LDL, and TG by approximately 25%, 25%, and 14%, respectively. Lovastatin was the only treatment to significantly affect CPK, increasing it by approximately 34%, although BSM, likely due to its content of 10 mg/dose of monacolins K and KA, showed a non-significant tendency to increase CPK by approximately 12%
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8874997/Human study2nutraceutical combinations seem to also play a role in the modulation of the lipid profile, and they have been clinically assessed. Several berberine-containing nutraceutical mixtures have been evaluated in clinical trials and have shown promising effects in patients with an abnormal lipid profile. One of them, conducted in patients with a low-to-moderate risk of hypercholesterolemia, has revealed that the combinations of nutraceuticals containing berberine, policosanol, and red yeast rice extract reduces the total cholesterol and LDL after 4 weeks. There were no significant changes in HDL, fasting glucose, and the serum triglycerides concentrations in any of the study groups, and the complex was safe and well-toleratedn patients with low-grade systemic inflammation, the oral administration of red yeast rice, berberine, and policosanol improved the lipid profile and attenuated the degree of systemic inflammation and endothelial injury. A significant reduction in total cholesterol, LDL cholesterol, high-sensitivity CRP, and endothelial microparticles were also observed in these patients [11]. The combination of berberine, with fermented red rice and chitosan, significantly reduced non-HDL-C, LDL-C, and apolipoprotein B after 12 weeks of treatment, compared to the placebo. On the other hand, there were no changes that were observed between the treatment arms in HDL-C, triglycerides, fasting plasma glucose, glycated hemoglobin (HbA1C), the waist circumference, and BMI
https://pubmed.ncbi.nlm.nih.gov/18789680/Human study - adjunct2Berberine significantly reduced the incidence of Radiation Induced Lung Injury, improved PF and decreased the levels of sICAM-1 and TGF-beta1. The exact mechanisms remain to be further explored. Of the 90 patients enroled, 43 in the control group and 42 in the trial group completed the study. The incidence of RILI was significantly lower in the trial group at 6 weeks and 6 months than that in the control group (45.2% versus 72.1% and 35.7% versus 65.1%, respectively)
https://link.springer.com/article/10.1186/1479-5876-12-22#Sec21Lab study1In summary, our study provides evidence that BBR inhibits lung cancer cell proliferation in vitro and in vivo, and that BBR may suppress lung cancer cell invasion and metastasis through inhibiting TGF-β1-induced EMT.Therefore, up-regulation of MMPs provides clues for tumor metastasis such as tumor-induced angiogenesis, tumor invasion and establishment of metastatic foci at the secondary site[38, 39]. Expression analysis of lung cancer cells also demonstrated that BBR treatment significantly down-regulated MMP. In addition to transcription factors, cell signaling molecules are also critical inducers of EMT in the context of development and in cancerScreenshot from 2025-06-23 20-39-39
https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.15214Lab study1 By binding to E-cadherin promoter region, snail transcriptionally regulates E-cadherin expression. There was a synergy in combination of BBR and gefitinib in this process (Figure 6I). Thus, this study suggests that therapeutic regulation of miR-34a-5p- and HOTAIR-mediated inhibition of EMT may provide an opportunity to control NSCLC growth and metastasis by the combination of BBR and gefitinibMoreover, our results unveiled a synergistic effect of combination of BBR and gefitinib in the regulation of HOTAIR, miR-34a-5p and EMT, and lung cancer cell growth. These implied the potential new molecular mechanism underlying the combination of BBR and gefitinib in controlling NSCLC cell growth. Substantial efficacy of BBR and other agents in combining has been reported to enhance potential anti-tumour activities in other studies as wellScreenshot from 2025-06-23 20-42-55
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655248/Lab study1In conclusion, we showed the anti-CSC effect of berberine on oral cancer via targeting miR-21, therefore leading to reduction of self-renewal and metastatic properties in vitro and attenuation of tumor growth in vivo. Our findings provided the evidence for using the natural berberine as an adjunctive therapy to traditional chemotherapeutics.Most importantly, we demonstrated that berberine potentiated chemotherapy by downregulation of miR-21. It has been suggested that miR-21 confers chemoresistance in cancer cells by regulating the expression of phosphatase and tensin homolog (PTEN) and programmed cell death 4 (PD4D4) [27, 28, 30], and berberine sensitizes cancer cells through PTEN/Akt signaling pathway [22]. Moreover, it was reported that berberine improves the therapeutic efficiency of cisplatin through miR-21/PDCD4 axis [45]. As such, it is possible that PTEN and PD4D4 are involved in the chemosensitizing effectScreenshot from 2025-06-23 20-43-56
https://www.mdpi.com/1424-8247/15/3/262Lab study1Furthermore, we found that the mutually enhanced antitumor effect of Andrographis and berberine is achieved through the co-regulation of DNA replication by verifying these genes at the transcriptional and post-transcriptional levels (Figure 6). These findings provide sufficient evidence for targeting DNA-replication-related genes as a promising new therapeutic strategy for CRC. While further analysis is needed in the future, we are excited that the combination of berberine and Andrographis may be a potential therapeutic strategy for patients with CRC in the futurTaken together, our data reveal a potent anti-tumorigenic property of berberine in a series of in-vitro, in-vivo, and patient-derived organoid experimental models and provide multiple layers of evidence supporting the enhanced anticancer effects of berberine combined with Andrographis. For the investigation of the potential mechanism, we profiled the berberine-induced gene expression alterations by RNA-sequencing to confirm that berberine predominantly inhibited DNA replication and to identify several novel target genes targeted by berberineScreenshot from 2025-06-23 20-45-06
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785675/Lab study1Taken together, our results indicated that berberine could inhibit CRC tumour growth partially via regulating the lincROR-Wnt/β-catenin regulatory axis. These findings provide a novel and epigenetic mechanism of the berberine-mediated anti-tumour activity and suggest that lincROR may be a potential or considerable target for berberine in the therapeutic application of CRC, which provides a strategy for the design of new anti-tumour drugs for CRC patients after our advanced validation. Strikingly, we found that the berberine groups carried smaller tumours when compared with the vehicle control groups (0.5% CMC-Na; NC), and the lincROR overexpressing partially rescued the in vivo tumourigenesis (Figure 6a). Moreover, a significant reduction in tumour volume and tumour weight was observed in berberine-treated groupsScreenshot from 2025-06-23 20-46-42
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10006790/Lab study1Conclusions: BBR significantly regulates the biological behaviors of osteosarcoma cells and inhibits the growth of osteosarcoma. The molecular mechanism may be associated with the modulation of MMP/NM-23 and MAPK/JNK signals. BBR may be a potential drug for the treatment of osteosarcoma.Our results showed that BBR inhibited the proliferation of MG-63 and U2OS cells in time- and concentration-dependent manners in vitro. BBR could also reduce the migration and invasion capacity of MG-63 and U2OS cells. The possible molecular mechanism could be that BBR down-regulates the expressions of MMP-2 and MMP-9. In in vivo experiments, it was found that the xenograft tumor was completely located in the capsule, without obvious invasion to surround tissues, lung metastasis and other distant metastases.
https://www.sciencedirect.com/science/article/pii/S1043661823001731#sec0080Lab study1The present study indicated that berberine exerted a remarkable therapeutic effect on breast carcinoma in 4T1/Luc mice tumor model with 100% survival rate, and had a positive regulatory effect on gut microbial disturbance and abnormal plasma endogenous metabolite levels in mice with breast cancer, which also provided a reference and basis for berberine treatment of breast cancer. In high metastatic breast cancer cells, berberine influenced the expression of E-cadherin, N-cadherin and β-catenin by affecting the HIF-1α protein, and then suppressed cell growth and metastasisImmunohistochemistry analysis indicated that the brown-yellow staining of β-catenin, E-cadherin and GSK-3β expression were remarkably increased in BBRL and BBRH groups, but not in DDP group. The expression of N-cadherin and MMP-9 decreased in BBRL and BBRH groups (Fig. 1I). The in vivo results provided evidence that the proliferation and metastasis of breast cancer could be inhibited by berberine, and had no obvious toxic side effects on organs. BBRH treatment was more effective to stop breast cancer development than the chemotherapeutic drug; it improved the survival rate of mice

Help grow the community

Join the Pubmedders subscriber base

Get our monthly email newletter – designed so you can give us your opinions, thoughts and feedback…

ALL contributions are invested into growing the site to help others.