BIRM

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

20 Replies

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  • 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

  • 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

  • Rich,

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

    -Patrick

  • Patrick,

    I agree with you.

    Rich

  • 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

  • I see the use of BiRM by those of us without tumors, somewhere between low PSA numbers to Castrate Resistant PSA's, again without tumors as being a Positive. Granted there is not a lot of Scientific Research--but what BIRM clearly does is cause Apoptosis, increase energy, and reduce fatigue.

    There is the Investment of the 1.2 Million by the NIH, to the University of Miami--so they feel it is worth a crapshoot. Though not really not enough money for much, but when combined with other University Monies, enough to further develop more in vivo, and in vitro data.

    I find the comments of those on Amazon, who rated this product to be most interesting, because these commentators though only I few were relate directly to Pca, almost all were related to cancer. Those taking taxane chemo and other Chemo all expressed major reductions in side effects of nausea, hair loss, and increased energy levels. And we have users, taking for multiple years. That runs into the low 1,000 dollar range--so is it blind faith, or results measured by the individuals????

    Interesting, as we have no studies, of worth that combines the use of Chemo to knock down tumors, in combination with BIRM, there could be a key use during Chemo, and upon the stopping of chemo with those having reduced remarkedly their tumors or eliminating them, to continue Birm, afterward, to effect the AR receptors, of what is remaining of Pca cells, as well as to cause Apoptosis, and reduction of those proteins that cause Angiogenesis. In my head I can form a number of pathway studies, to follow, the current ones being planned. But this is not my job. My job is to beat this disease, or maintain a durable Remission

    But, even without enough information, since I am ingesting, a multitude of Supplements that have shown to cause Apoptosis of Pca cells, In Vivo, and In Vitro, there may be a synergistic affect, that cannot be determined from hence it might come from, as the permutations, and probability of finding out what works with what is enormous, for me.

    AS a user of an ADT[5] blockade, I obviously experience much in the way of side effects, related to energy loss and fatigue, which I try to reduce thru exercise in the gym, and other energy boosting supplements. So I can measure the effects reported by users on Amazon, and if my energy levels increase, and my Fatigue decreases, as reported by those on Chemo, it is worthwhile for me to experiment with this BIRM material.

    So I have ordered it! I have in the past been disappointed in some supplements and have eliminated them, others are part of a daily routine. It is worth it to me, the 47 dollars, to give this Puppy a 30 day evaluation.

    I am not a Doctor, but I play one at home--so I will carefully monitor my body reactions, such as Temp, Blood Pressure, weight etc. and most importantly how I feel. I know the difference between the placebo effect, and an actual benefit felt. I cannot measure this BIRM as to PSA reduction, as I am still maintaining undetectable numbers, but others like Gusgold, who have small PSA numbers, and are in the pre-castrate resistant range should if using, sequence their PSA tests to confirm or deny a benefit. Even those whose PSA Numbers are above 4, without any tumor activity, can do the same if they wish to experiment. I can only measure as I said above fatigue, and energy levels. And if is all it does, is to counteract the effects of the side effects of my ADT[5], it will be worth it to me.

    I will let you all know what I feel, though I will not be able to measure. Anyway I am to old to wait for 5 years of research.

    Nalakrats

  • 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

  • It is a bit of a crap shoot, The papers written, are sketchy. Yet this has been used locally in Ecuador, to fight all cancers, for 13 years. Local reports, believable or not. claim cures and major stopping/halting of further tumor growth. But we do not see much evidence of tumor reduction.

    The fact that the Amazon users of this BIRM, whose actual composition was Identified by Patrick Oshea, have been married to this material, for years. Upon reading the 54 Comments/readings of users/buyers on Amazon, is enough for me to pull the trigger. Order expected to arrive in 4 more days. Users say they notice fatigue reduction during chemo, hair loss stopping, nausea being alleviated, and those not on chemo report increased energy, and fatigue from their cancer, HIV, and other Viruses. Reductions in PSA/and Apoptosis have also been recorded, some from Ecuador, some on the Amazon site. Probably those without tumors, in bone or soft tissue.

    As I have said upon personal use, If I get an increase in energy boost, this BIRM, would be valuable to me.

    Since it is to show results in 2 weeks, by my birthday on May 4th--I should know, if it is causing some positive effects. I cannot measure it against PSA, as I do not have a measurable amount at this time. Others who plan to use, have some PSA + numbers, and their reports would be more important than me getting an energy boost. In a short time we should have some personal data.

    Nalakrats

  • 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

  • Interestingly Alan, would be to go to the Amazon site and read the 54 reviews---you might come to another theory--as those under Chemo and BIRM, had successful treatments. Success for some were remissions, some were reductions in disease, and others had a halting of spread.

    As I said my experimental use, will be to see if I have increased energy, less fatigue, and knowing I have another substance on board that has negative affects on cancer cells in Vivo, and in Vitro.

    The under the radar investment by the NIH, should be enough to take a peak at it. I am my own Doctor, and will gladly report any subjective physical improvements. Others I think who are jumping in have some measurable PSA, and they can do a 30 day experiment. So this stuff either has value, or it does not. It is not worth having an intellectual argument when there are so many unknowns, and nobody has died from it.

    Nalakrats

  • 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

  • True Alan---I am just saying we do not know much, about this---and only use of something that seems to cause no harm, so far, is worth a shot. I ain't waiting for Miami Univ. and 3 years of study, when I and others can do their own study, now.

    By the way, exercising the hands does help with the Trigger Finger, I am searching the house for my gripper--but I am using something in the gym. Also I will report on a brand new Hyaluronic Acid Product, that is loaded up with 2 types of Collagen, and after 3 days there is a difference to the positive----need about a month on this and will report regarding the 30+ respondents I had. Hopefully with some conclusions, which will probably line up with yours.

    Nalakrats

  • 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

  • I have clearly said I was doing my own thing, I identified a new Material. I asked Patrick Oshea to research it. There is no mis- leading, As I often say I am not a Doctor, but play one at home. My 50 years, with Nutritional Healing, allows me to have leeway on myself. Myself!

    And by the way do you know where they found Aspirin in the 1800's.

    One may find a nugget among, the least likely places.

    I cannot address the chemical content, until I get my hands on it. Why not wait to when I have a chance to do a label analysis, and if Need be, I can put it thru High Pressure Liquid Chromatography, to identify the molecules. There could be new molecules, that have no history

    Hope you appreciate aspirin as I do.

    Nalakrats

  • 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

  • Thanks--I do not mislead. The Prostate Cancer Sites I contribute to is a 'free ministry for me'. Helping others, if I can, I do the best I can, drawing from a vast amount of experience in Organic Synthesis Chemistry, Food Science, Diet and Nutrition, having masters degrees in such, and practicing Nutritional Healing as I have said for 50 years. I am/was a research scientist, across a number of areas, related to ingestion of various substances and how they play, in the body.

    I am published 6 times, and have helped people cure heart disease, high blood pressure, a-fib, bone loss, etc. I am a bit flustered with Pca, but I intuitively know certain things, and we are dealing with dozens of diseases. As an aside I am the discoverer of Teanine, used as a sleep aid, and did the original synthesis, in 1967, as a research chemist. So I have a history, and would not want to add my resume, as I do prefer anonymity.

    As to BIRM: as I said, Patrick Oshea, was asked by me to please research it. He put out a good bit of information, and concluded he would not at this time use it, for the same reasons we are all skeptical about it. We have basically no clinical research, from respected organizations. Miami University is not on the top 50, relative to caner research.

    My BIRM should arrive next week. They?, cannot sell this without a label declaration, following FDA laws for ingesting supplements, etc. Patrick Identified the botany names. I will evaluate the label, then research further the botany, if I can find it. As I have said I have availability of an High Pressure Liquid Chromatography computerized Identifier of chemical compounds at my local Hospital. May not be of value as I expect we will find things not yet known. That is what happened with my work on Theanine, as I did much of the work on the high molecular weight Galate Polyphenols, in green and black Tea, and this amino acid showed up that nobody at that time knew about.

    Not trying to be overly long, here, but I plan to be very careful. The usage is 2 mls twice a day. I will probably, start with 1 for a week, and then go to 2, if I do not detect any negatives.

    I have gone back to Amazon and re-read the comments, by users, some using for years. Alan Meyer brings up a point that has to be given credence. If it reverses the side effects of Chemo, is it reducing the action of Chemo? I can add, if BIRM can do what the respondents on Amazon say--I can add will BIRM, eliminate the side effects of ADT, and in so doing reduce its effectiveness.

    So it is a bit of a crap shoot. But so were a lot of things. I am aware of the cautions to be taken, especially interactions that are negative to any of my other supplements. And I never asked anyone to go get this BIRM. I just identified it from some research. And put it out there, for our group to read. I think it was Gus who said it might be better than Gator Blood, in his humor, and was purchasing. I actually waited 3 more days before doing so.

    I plan to do weekly PSA's which Medicare will not pay for at AnyLabTest--as they use the same lab that my Urologist uses. To gather empirical data we have to measure something. If it acts against my ADT-5 Block, and causes my PSA to be detectable, well I would stop, obviously. I think one who plans to use, has a PSA of .12, which is measurable, and might be a good subject to see if there is an effect, up or down.

    As I said I am looking for a further energy boost, and less fatigue. The reports of Apoptosis[cell death of cancer, in vivo, and in vitro, interests me.

    I have reduced Fatigue and increased Energy, by the use of Liposomal C, and Zyflamend, plus Heavy Gym work. What is left is some minor aches and minor pains, which whom would not have, at the age of 73, without cancer???

    Anyway I have said enough about an unknown. My personal experimental evaluation, on myself, will begin when I get my hands on it.

    Nalakrats

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

  • Sovereign Laboratories--on Amazon---true Liposomal. Issues with Dr. Mercola's

    Nalakrats

  • 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

  • 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.

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