Berberine as a cancer treatment

Berberine as a cancer treatment

Berberine has been shown in research to work along a number of quite separate pathways against cancer; it reduces blood sugar levels, it reduces inflammation, boosts immune response and attacks certain pathogens; it blocks Akt and mTOR, while promoting AMPK and weakening the cancer cells, and acts as both a chemo-sensitiser and a radio-sensitiser.

Indeed, with some oncologists starting to use diabetes drug metformin in the fight against cancer because it cuts blood sugar and also affects the mTOR pathway, it is important to note that the herb berberine does everything that metformin does, and more. Much more!

What is Berberine?

Berberine is an isoquinoline alkaloid component of many medicinal herbs, such as Goldenseal (Hydrastis Canadensis), Goldthread (Coptis chinensis), Chinese Isatis (Isatis tinctoria), Oregon grape root (Berberis aquifolium) and Barberry bark (Berberis vularis).  

Berberine and pathgogens

Expert Herbalist, Alan Hopking, described Berberine a few years ago to CANCERactive thus:

"Berberine has an action against some pathogens that is actually stronger than that of antibiotics commonly used. It has been found to inhibit candida albicans and prevents the overgrowth of yeasts, a common side effect of antibiotic and chemotherapy use. It has anti-microbial action against E coli, and Staphlococcus aureus. Berberine has been shown to inhibit the growth of Giardia, Trichomonas vaginalis, Entamoeba histolytica and Ieishmania donovani. As Goldenseal it kills Helicobacter pylori."

Berberine and the immune system

Not surprisingly, it is known to be a powerful auto-immune treatment because many auto-immune diseases involve yeats and other pathogens. This fascinating alkaloid increases blood supply to the spleen and thus increases immune response

It has also been shown to activate macrophages in a number of ways. Coupled with its ability to inhibit tumour formation, it seems Berberine possesses some anti-neoplasic activity."

Berberine, in a 2020 review of research (18) was reported to directly suppress pro-inflammatory T helper cells which over produce cytokines and interleukin. This resulted in an increase in macrophage activity. 

Berberine and health

Berberine has further general health benefits:

  * Berberine has a strong hypoglycemic (blood sugar lowering) benefit. It also has anti-obesity benefits as it can reduce blood fats too (see below). A review of Berberine research showed that its action was related to inhibition of mitochondrial function, stimulation of glycolysis, activation of the AMPK pathway and blocking of the LDL receptor expression (17).  

  * Berberine can reduce blood pressure and improve blood supplies in diabetic patients (15). Compared to Metformin, it had a statistically significant increased benefit. It has been used in Medicine in the Far East for centuries. In one study it was shown that taking 0.9 gm a day could make Amlodipine (a calcium channel blocker) work better.

  * Berberine can reduce blood lipids - not just cholesterol and especially LDL, but triglycerides too. 1,000 mg a day for 3 months was the research dose. In the meta-analysis Berberine was shown to increase 'good' HDL (16).

Berberine and cancer   

Berberine has many benefits like those above which help in the fight against cancer:

   * Anti-inflammatory benefits. Berberine has the ability to inhibit Cox-2 expression. Several studies show this attribute in vitro and in vivo (1, 2). This is one of the major reasons behind its inhibitory benefits against cancer. Metformin does not exhibit this benefit.

   * Anti-infectious benefits. Berberine has actions against many pathogens; for example, against the recurrence of Clostridium difficile(3), and it has also been shown to attack the membranes of Candida albicans (4) - common yeast; it has action against stomach cancer parasite H. pylori. And more!

    * Blood sugar reduction. We have an article entitled '20 links between sugar and cancer', on this website. 18 of these are from top Professors and Scientists at top Medical Schools in the West. Berberine reduces glucose production in the liver and is as powerful as both the pharmaceutical drugs, metformin and glibenclamide in controling blood glucose levels. It can also help in weight loss programmes. Blood sugar levels and excess weight are both linked to increased cancer risk and recurrence.

     * Berberine reactivates AMPKCrucially, it changes the way cells metabolise their fuel - it works on the ’metabolic master switch’, an enzyme inside all cells called 'AMP-activated protein kinase', or AMPK, which is involved in a great many biochemical pathways. In cancer cells there is a marked decline in the AMPK enzyme which allows Akt and mTOR to be expressed. Berberine can restore and preserve the integrity of the AMPK enzyme and even turn it back on, encouraging the re-start of normal aerobic mitochondrial activity (7). It can thus block both the m-TOR and Akt cancer pathways.

   * The blood sugar lowering activity of Berberine is known to be independent of insulin. Its hypoglycaemic effect is caused by this inhibition of mitochondrial activity and the stimulation of the AMPK pathway. These actions make it useful in both diabetes and cancer treatments.

   * Berberine is a chemosensitiser; and radiosensitiser. Berberine can act on its own, but because it also attacks and weakens cancer cells, it can also improve the effectiveness of chemotherapy by enhancing chemosensitivity(5) and restricting cancer cell drug resistance. It is known to  even restrict cancer stem cell drug resistance .  Berberine also improves radiotherapy by enhancing radio sensitisation of cancer cells(6).

   * Berberine reduces drug resistance - Most importantly, it helps drugs work longer by helping overcome cancer cell drug resistance. For example, it reduces the build up of resistance to drugs such as Lapatinib in HER2 breast cancer (13), and Doxorubicin in melanoma, and generally with tDoxorubicin by increasing the effect of neutrophils (19). Similarly, berberine can reduce CD47 expression and increase the effectiveness of Rituximab in Lymphoma treatment. 

It truly has multiple actions in the fight against cancer. No wonder Chris Woollams uses it in different ways in many of the successful Personal Programmes he builds for cancer patients!

Berberine and specific cancers

There are over 700 quality research studies conducted on Berberine and cancer and research is gathering momentum. For example:

1. Berberine and Colorectal Cancer - Berberine has a number of important actions. Its ability to reduce blood sugar levels. A strong anti-inflammatory action against Cox-2. And it has a number of strong digestive benefits and the ability to kill yeasts and pathogens. Combined these give it a strong influence in colorectal cancer where it can limit invasion and metastases(8).

A 2017 study showed that Berberine could inhibit the metastases and invasion of colorectal cancer cells both in vivo and in vitro in three ways - by restricting Cox-2, by reducing phosphorylation and by restricting MMP expression(10).

2. Berberine and breast cancer - a 2016 study on breast cancer cells showed that berberine and curcumin worked in combination to cause apoptosis (cancer cell death) and autophagic cell death(9).

Berberine prevents cell growth and induces apoptosis in breast cancer cells (Kim JB et al 2010; Patil JB et al, 2010); In 2016, a study by Lanzhou University Medical School in China showed that because Berberine could turn the AMPK enzyme back on, Berberine could correct breast cancer cells.

3. Berberine and Brain Cancer (GBM) - Berberine inhibits gene expression and enzyme activity necessary for glioblastoma and astrocytoma growth (Wang DY et al, 2002). This is not the first time it has shown effect with brain tumours. One study showed it might be a useful adjunct in PDT - in vitro experiments showed using berberine alone, or in combination with laser treatments, on glioma cells were both effective (Chen KT et al, 1994). In 2004 it was shown to be a sensitizer of glioma cells where it increased the success of radiotherapy in brain tumours (Wallace J et al, 2004).

A 2008 study explained that berberine triggers apoptosis in glioblastoma cells through the mitochondrial caspases pathway (Eom KS et al 2008).

In 2009, research reported that berberine kills glioma cells through several mechanisms: “Cytotoxicity is attributable to apoptosis mainly through induced G2/M-arrested cells, in an ER-dependent manner, via a mitochondria-dependent caspase pathway regulated by Bax and Bcl-2” (Chen TC et al 2009).

A 2015 study showed that it aided the action of temozolomide against glioma (brain cancer).  Indeed part of the study suggested it was also effective in its own right even beating the effects of Temozolomide.

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Berberine enhanced the activity of carmustine, a chemo drug often used on brain tumours. Berberine in culture or in rats given cancer tumours, on its own produced a 91% kill rate in cell cultures, compared to 43% for carmustine. When the two were combined the kill rate rose to 97% (Zhang, RX et al, 1990).

4. Berberine and prostate cancer: Berberine has been shown to inhibit metastatic activity in prostate cancer cells. In particular Berberine seems to be one of the few compounds that inhibits the EMT program which causes metastases to bones (14). Neither hormone therapy nor chemotherapy nor radiotherapy has any action on bone metastases in prostate cancer but berberine does show effect. 

5. Berberine and other cancers: 

 In 2011, a review of the anti-cancer effects of berberine concluded that it was a promising, safe anti-tumour agent with a number of potential therapeutic uses (11).

 * Berberine sensitizes lung tumor cells to radiation (Peng PL et al 2008, Liu Y et al, 2008).

 * Berberine is cytotoxic to cervical cancer cells (Lu B et al, 2010);

 * Berberine inhibits cell growth in pancreatic cancer cells by inducing DNA damage (Pinto-Garcia L et al, 2010).

 * Berberine triggers cellular suicide in tongue cancer (Ho YT et al 2009).

Yet more ways Berberine works against cancer?

Berberine seems to work in other ways too:

  * Berberine inhibits an enzyme called arylamine N-acetyltransferase (NAT) that is thought to initiate cancer (Hung CF et al, 2000).

  *  In 2007 there were conclusions that berberine acts “through several ways, such as regulating apoptotic gene expression, suppressing the formation of tumor angiogenesis [and blocking signal transduction pathway” (Yang J et al 2007).

  * In 2010 showed that Berberine could inhibit NF-KappaB and other compounds that help cancer cells survive by slowing apoptosis (Pazhang Y et al 2010).

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Metformin and Berberine can work together against cancer

Berberine seems to have so many benefits against cancer, well beyond its sugar control. But Metformin also has sugar controlling benefits and acts on AMPK - it is the ’diabetes drug’. For this reason, many users take an either/or approach. That seems to be quite wrong. Actually Berberine and Metformin seem to enhance each other’s activity. For example, there is a study with Non-Small Cell Lung Cancer (NSCLC) showing exactly that (12). They work together in vitro and in vivo against a particularly nasty cancer.

Dosage of Berberine in cancer therapy

Berberine seems to be dose dependent and research indicates that low doses may be totally ineffective, and may even cause problems.

The cancer inhibiting doses in research seem to start at 3 x 500 mg a day. Some people use 2,000 mg.

Berberine can cause a heavy heart beat and probably should not be taken long-term, although there is little evidence for this warning.

Berberine is, however, as powerful as pharmaceutical drugs. There are a few concerns about long-term usage causing metabolic changes. More work is however needed on this. 

Go to: How Berberine helps fight TNBC

Go to: Berberine pre-sensitises cancer cells to chemotherapy and radiotherapy

Go To: Berberine has a strong effect against brain cancer

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References

1. http://iv.iiarjournals.org/content/19/1/247.abstract

2. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0069240

3. https://aac.asm.org/content/59/7/3726

4. https://bmccomplementalternmed.biomedcentral.com/articles/10.1186/s12906-017-1773-5

5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535724/

6. https://www.spandidos-publications.com/ijmm/30/5/1166/download

7. https://www.sciencedirect.com/science/article/pii/S2211383512000871

8. https://www.ncbi.nlm.nih.gov/pubmed/25954974

9. Kai Wang et al: 7 Jan 2016; Nature, Scientific reports 26064

10. Xuan Liu, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425560/

11. A promising anti-tumour agent

12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742731/

13. https://www.tandfonline.com/doi/abs/10.1080/15384047.2016.1210728

14. http://www.medsci.org/v12p0063.htm

15. https://pubmed.ncbi.nlm.nih.gov/28515053/

16. https://pubmed.ncbi.nlm.nih.gov/23512497/

17. Jun Yin et al; Endocrine Metabol; 2008 June 8;  https://pubmed.ncbi.nlm.nih.gov/18537696/

18. J Cell Mod Med; Dec 24, 2020, 23; https://pubmed.ncbi.nlm.nih.gov/33135395/

19. Berberine reverses cancer cell resistance to Doxorubicin; Shuhui Zhang et al; Front Pharmacol 2020, 29 Jan; https://www.frontiersin.org/articles/10.3389/fphar.2019.01658/full

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