BIRM

[pjoshea13]

BIRM [Biological Immune Response Modifier] is an extract from Kalanchoe gastonis-bonnieri, found in the Amazon forest of Ecuador [1] [3].

Nalakrats brought it to my attention. It can be purchased via Amazon.

There are only two PCa studies on PubMed. The first [2] was in 2003 from the University of Miami School of Medicine. The second [3] was published in 2016, i.e. after a gap of 13 years. Both studies were led by Dr. Bal Lokeshwar, who moved from Miami to Augusta University, GA in 2014. Perhaps there was a funding issue in Miami, but, clearly, Dr. Lokeshwar has retained an interest in BIRM. The paper was actually written by N. Shamaladevi, University of Miami, with co-authors from Japan & Ecuador.

In the interim, Dr. Lokeshwar's name appears on numerous papers, including two dozen PCa papers. (As you can see, I am trying to drum up interest in what is a little-known little-studied supplement. Lokeshwar has been involved in some interesting PCa studies.)

In the earlier study [2], "The cytotoxicity of BIRM in four human and one rat CaP cell line was evaluated". The four human cell lines are not named in the Abstract.

"BIRM inhibited cell proliferation and clonogenic growth of the CaP cells (IC(50) about 8.0 microl/ml). It increased cell accumulation in the G(0)/G(1) phase by 33.8% and decreased the proportion of cells in S phase by 54.6%."

In addition: "The in vivo efficacy of BIRM was evaluated in rats with subcutaneous tumor implants of Dunning EGFP-MAT LyLu cells." i.e. human cell lines were not used in the rat part of the study.

"Treatment of MAT LyLu tumor-bearing rats with BIRM by oral gavage resulted in a significant decrease in tumor incidence (50%), tumor growth rate (18.6+/-1.3 days for 1 cc tumor growth in control rats and 25.7+/-2.6 days in BIRM-treated rats), and only one out of six BIRM-treated rats versus four out of six in the control group developed lung metastasis."

In the recent study:

"In androgen receptor (AR)-expressing PCa cells BIRM was 2.5-fold (250%) more cytotoxic in presence of androgen (DHT) compared to cells grown in the absence of DHT. In AR-positive cells (LAPC-4 and LNCaP) BIRM caused a dose and time-dependent down-regulation of AR and increased apoptosis. Exposing cells to BIRM did not affect the synthesis of AR and AR promoter activity but increased degradation of AR via proteasome-pathway."

i.e. while BIRM degraded AR, it did so more effectively when AR was active.

"BIRM caused destabilization of HSP90-AR association in LAPC-4 cells."

HSP90 is a heat shock protein. It acts as an AR chaperone, making the AR more difficult to target. If BIRM interferes with its chaperone duties, BIRM might be useful in therapies known to induce HSP90.

"BIRM dosed by oral gavage in mice bearing PC-3ML tumors showed selective efficacy on tumor growth before tumors are established but limited efficacy when treated on existing tumors."

That's a disappointment.

From the full text:

"BIRM is extensively used in Western

Hemisphere mainly as Herbal immune booster, as by th e

manufacturer (Ecua-BIRM Inc., Quito, EC and on their

website [WWW.EcuaBIRM.Com]. In addition, as per the

manufacturer of BIRM, this product has been dispensed

as a complementary medicine for ailments such as AIDS,

lupus, arthritis related psoriasis and various treatment refractory

cancers."

Unfortunately, PubMed has no supporting studies for BERM use under these conditions.

-Patrick

[1] en.wikipedia.org/wiki/Kalan...

[2] ncbi.nlm.nih.gov/pubmed/127...

Cancer Chemother Pharmacol. 2003 Jul;52(1):59-66. Epub 2003 May 7.

An orally active Amazonian plant extract (BIRM) inhibits prostate cancer growth and metastasis.

Dandekar DS1, Lokeshwar VB, Cevallos-Arellano E, Soloway MS, Lokeshwar BL.

Author information

Abstract

PURPOSE:

Poor efficacy of conventional chemotherapeutic drugs against metastatic hormone-refractory prostate cancer (CaP) drives patients to try "alternative medicine". The antitumor activity of one such agent, "BIRM" (biological immune response modulator; "Simple Ecuadorian Oral Solution: an extract of an Amazonian plant"), was characterized in vitro and in vivo using established CaP cell lines and a tumor model.

METHODS:

The cytotoxicity of BIRM in four human and one rat CaP cell line was evaluated using cell proliferation-inhibition and clonogenic survival assays. BIRM-induced apoptosis, alterations in cell cycle phase progression and inhibition of the extracellular matrix-degrading enzyme hyaluronidase were also investigated in these cells. The in vivo efficacy of BIRM was evaluated in rats with subcutaneous tumor implants of Dunning EGFP-MAT LyLu cells. The active species in BIRM were characterized by gel filtration chromatography.

RESULTS:

BIRM inhibited cell proliferation and clonogenic growth of the CaP cells (IC(50) about 8.0 microl/ml). It increased cell accumulation in the G(0)/G(1) phase by 33.8% and decreased the proportion of cells in S phase by 54.6%. Apoptotic cell death in BIRM-treated cells was associated with activation of cell death-associated caspases. BIRM inhibited the activity of hyaluronidase, a hyaluronic acid-degrading enzyme, at 1 microl/ml. Treatment of MAT LyLu tumor-bearing rats with BIRM by oral gavage resulted in a significant decrease in tumor incidence (50%), tumor growth rate (18.6+/-1.3 days for 1 cc tumor growth in control rats and 25.7+/-2.6 days in BIRM-treated rats), and only one out of six BIRM-treated rats versus four out of six in the control group developed lung metastasis. Three active ingredients in BIRM with a relative molecular mass (Mr) of >or=3500 were identified by ultracentrifugation and gel filtration chromatography and were found to be resistant to proteinase and heat (100 degrees C).

CONCLUSION:

The plant extract BIRM contains antitumor compounds of Mr >or=3500 with potent antiproliferative activity in vitro and in vivo against prostate cancer cells.

PMID: 12734674 DOI: 10.1007/s00280-003-0612-1

[Indexed for MEDLINE]

[3] ncbi.nlm.nih.gov/pubmed/277...

FULL Text can be accessed.

Oncotarget. 2016 Dec 20;7(51):84201-84213. doi: 10.18632/oncotarget.12393.

The andean anticancer herbal product BIRM causes destabilization of androgen receptor and induces caspase-8 mediated-apoptosis in prostate cancer.

Shamaladevi N1, Araki S1,2, Lyn DA1, Ayyathurai R3, Gao J4, Lokeshwar VB5, Navarrete H6, Lokeshwar BL4.

Author information

Abstract

BIRM is an anticancer herbal formulation from Ecuador. Previous study established its antitumor and antimetastatic activity against prostate cancer models. The activity of BIRM against human prostate cancer (PCa) cells was investigated to uncover its mechanism of antitumor activity. In androgen receptor (AR)-expressing PCa cells BIRM was 2.5-fold (250%) more cytotoxic in presence of androgen (DHT) compared to cells grown in the absence of DHT. In AR-positive cells (LAPC-4 and LNCaP) BIRM caused a dose and time-dependent down-regulation of AR and increased apoptosis. Exposing cells to BIRM did not affect the synthesis of AR and AR promoter activity but increased degradation of AR via proteasome-pathway. BIRM caused destabilization of HSP90-AR association in LAPC-4 cells. It induced apoptosis in PCa cells by activation of caspase-8 via death receptor and FADD-mediated pathways. A synthetic inhibitor of Caspase-8 cleavage (IETD-CHO) aborted BIRM-induced apoptosis. The effect of BIRM on AKT-mediated survival pathway in both AR+ and AR- negative (PC-3 and DU145) showed decreased levels of p-AKTser 473 in all PCa cell lines. BIRM dosed by oral gavage in mice bearing PC-3ML tumors showed selective efficacy on tumor growth; before tumors are established but limited efficacy when treated on existing tumors. Moreover, BIRM inhibited the LNCaP tumor generated by orthotropic implantation into dorsal prostate of nude mice. Partial purification of BIRM by liquid-liquid extraction and further fractionation by HPLC showed 4-fold increased specific activity on PCa cells. These results demonstrate a mechanistic basis of anti-tumor activity of the herbal extract BIRM.

KEYWORDS:

Anti-cancer herbal preparation; androgen receptor; caspase-8; chemoprevention; prostate cancer

PMID: 27705939 DOI: 10.18632/oncotarget.12393

[Dan59]

Patrick, as always thank You for the research you do for us. I just ordered the cancer bush Sutherlandia Frutescens, that you suggested to block the ptch1 pathway after re reading your post there. all is well

[BigRich]

Patrick,

" BIRM dosed by oral gavage in mice bearing PC-3ML tumors showed selective efficacy on tumor growth; before tumors are established but limited efficacy when treated on existing tumors." However, most of my brothers on this site have existing tumors. I wonder how much limited efficacy on existing tumors.

I think this should be investigated with their medical doctor by individuals whose tumors have not been established.

Rich

[pjoshea13 in reply to BigRich]

Rich,

After 13 years, seems that I shouldn't expect much. I need to see something more possitive before I buy some.

-Patrick

[BigRich in reply to pjoshea13]

Patrick,

I agree with you.

Rich

[Sisira]

Thanks are due to Patrick, Nalakrats and Gusgold for their joint efforts on the BIRM. I fully agree with the "Purpose" stated in Patrick's post - "Poor efficacy of conventional chemotheraputic drugs against metastatic hormone refractory prostate cancer drives patients to try alternative medicine" This is a stark truth and also a need of the hour. But it is also equally important that we should remain in the scientific domain when we look at them because too often they are surrounded by mystery.

Patrick's explanations are on sufficient scientific footing and his research articles have already proved to be very sound and useful to us in many ways. When we are bent too much on scientific research we may not like to pay sufficient attention to herbal medicine whilst thinking of chemicals and test tubes producing all drugs. The popular brand "Taxotere" ( Docetaxel ) drug used in chemotherapy for advanced metastatic prostate cancer is a "taxane" which is a "plant alkaloid" ( Taxanes are made from the bark of the Pacific Yew tree ( taxus ). So there is nothing to be surprised when BRIM is made as an extract from a plant in the Amazon forest.Things have been made simpler when the price has been quoted as $47 when ordered from Amazon and thank you Gus for finding out the dosage as 2ml twice per day.

I also read the news letter article by clicking on the web address provided by gusgold and was dismayed by its presentation on BIRM. I hate to look at "Mystery Cures" ( title given to the article ) surrounded by family secrets. It is so difficult to unearth the truths - which plant in the jungle? which species? Natural or grown with chemical fertilizers ? Is the extract one substance or a compound? No sufficient disclosure for any of the important questions. May be due to financial interests or traditional family secrets. Under such circumstances it is unwise to buy "snake oil" for a mystery cure or for whatever it is worth, we may desperately gulp down a dose even if it has the same effect as "Coca-cola" and nothing more.

I appreciate the point raised by BigRich too.

Anyhow, let us look at it positively if we have stronger reasons to rely on this new product which has come to the market. Certainly not as a "Mystery"!

Sisira

[Sisira]

Well justified. Your approach is commendable. Waiting eagerly to know the efficacy of BIRM from the intended users including yourself. Do you have any background information regarding the manufacturer of this unique product and most importantly the chemical analysis of the extract?

Appreciate the time you are investing on research for the common benefit of all of us.

Sisira

[AlanMeyer]

Nalakrats wrote:

" Users say they notice fatigue reduction during chemo, hair loss stopping ..."

The hair loss stopping during chemo raises a bit of a red flag for me. My understanding of chemotherapy is that it interferes with mitosis, i.e, cell division. The effect is apparent in many areas of the body but it is the frequently dividing cells that are most likely to be caught in the process of cell division and hence killed by the infusion. Hair cells and some of the cells of the stomach are frequently dividing, hence the patient experiences hair loss and nausea.

If hair loss is stopped, might not that mean that BIRM is protecting the hair cells against chemo? And if so, might it also be protecting the tumor cells against chemo? That wouldn't mean that the compound doesn't have anti-cancer properties but it might mean that it has anti-chemo properties and shouldn't be used during chemotherapy.

The anti-nausea behavior raises the same red flag, though it could mean that the compound calms the stomach rather than that it protects it from chemo.

So I would be inclined not to use this compound during chemo.

Alan

[AlanMeyer]

I'm not questioning the value of BIRM as an anti-cancer compound, I'm just questioning whether it should be used during chemotherapy.

An analogous problem is Vitamin D and radiotherapy. There's significant evidence that Vitamin D is useful in preventing and treating cancer. However it is a strong anti-oxidant that can interfere with the oxidation damage that is caused by x-ray ionizing molecules inside the cancer cells.

Alan

[Sisira]

Dear friend Nal,

There are thousand and one medicine and stories not only from the Amazon forest but also from Himalaya in In India famous for hermits who meditate and discover miracle medicine through spiritual powers for all kinds of ailments. There are lots of people who use them and also praise with blind faith but as for me I don't believe because their efficacy is based only on anecdotes and not on any worthwhile analysis.

I searched the internet to check with the manufacturers who market the product BRIM through Amazon.com to check the properties of this medicine. Many of them have described it as an immunity booster and not a word about anti-cancer action. One or two have related its action with PCa.

The simple question I have asked from you, you have failed to answer - the chemical composition of the extract? In our country even a bottle of water sold in the market should show the chemical composition. As Alan has rightly pointed out suppression of side effects of other important treatments may be achieved with more harmful biochemical action in the meidium/longterm due to unknown chemical reactions.

I respect your personal choices and experimentation but in the absence of any ( not even an effort ) scientific proof, bringing such matters for open discussion may mislead others.

Sisira

[Sisira]

I think it would have been better had you done your original posting on BIRM after completing your team work with a thorough analytical study on the product coming from a mysterious forest. At least the product is surrounded by mystery if not for the forest! After reading your first post I was motivated to place an order for a bottle but I hesitated and asked from myself why should I buy it without knowing "who produces what?". With due respect to you, honestly I felt for a while I was misled. I know it was not your intention.

Sisira

[gusgold in reply to Sisira]

I thought the same thing...that Nalakrats has a financial interest in BIRM to pay for his monthly trips to Costa Rica. Upon further investigation BIRM is distributed by Kratsnala Labs LLC in the U.S. Kratsnala Labs only other product is a treatment for PCa called GB (Gator Blood). So, I don't see any evidence that Nalakrats has a financial interest in Birm.

Gus

[paulofaus]

Nal, could I ask which brand of Liposomal VitC you use?

[Moespy]

4 years after RP and a little over a year after 38 radiation sessions my PSA rose in February from undetectable to .1. I started BIRM 2 days ago along with the many (26) supplements added 5 weeks ago. I have informed my Hopkins doc of all of this and received no objection. I will report back on my PSA result when I receive it in Mid May. Just waiting for the PSA to rise again as I did after RP and now after bed radiation is much less attractive and scary to me than trying to keep it from moving with supplements and BIRM.

[Hidden in reply to Moespy]

So Moe I didn't see a reply on the BIRM you tried 2 years ago. Did it work for you? Would you recommend it to others?

[Moespy in reply to Hidden]

Hi Rudy, I stopped taking BIRM a long time ago (year?). Supply ran out and I couldn't source it for a couple months and just never went back. I still take many supplements just no longer take BIRM. Didn't notice any difference on or off BIRM regarding physical well being or PSA levels. Jim

[Hidden in reply to Moespy]

Thanks for the reply.

[Hidden in reply to Moespy]

Do you suffer from fatigue and if so what do you take for it??

[Moespy]

I am fortunate to be 7+ years in and still no ADT or other drugs. MedOnc and RadOnc say I may be able to get another year before we do any treatment. I am hoping for SBRT spot shots for found mets and then move on to ADT/Abiraterone.

[Ptclassics]

Hal have you ever listed the sups you take you said you have elimeated may I am on many now and may be wasting time which I do not have 8 years Mestatic Psa 60

[Ptclassics]

Nal what happened when you took brim you can no longer find it on eBay or amazon

[lewicki]

Is it possible you could list your supplements and dosages for me. Thanks

Very much appreciated. Any success with BIRM ?