The following post provides information and NON-MEDICAL advice I've come across that I'll be presenting to my oncologist tomorrow. I thought it might be of value for others among us to consider, to further research (I provide citations), to comment on, and/or to speak to their doctor(s) and oncologist about. Bless you all and, most especially, the wonderful administrators who devote so much of their lives to helping us find a better place to be!
In my readings, I’ve come across a number of sites I consider valuable with regard to the possibility of treating me (and possibly others). I would sincerely appreciate your reviewing the information below (and possibly the cited sites), and letting me know if you believe we can move forward with any of these as possible supplemental treatments.
* A general conclusion of mine, from what I’ve read, is that anything that both induces apoptosis and appears to have a direct beneficial effect on CLL, as noted in these and many other studies, could help by reducing my dosage of any targeted therapy treatment and also minimizing my adverse reactions. Therefore, I would like to know:
—Do you agree, with this statement?
—Do you believe that any of the belowmentioned items could be used to supplement my therapy and, if so, which?
—Are you aware of any other possible natural supplements that could be similarly beneficial?
—If you believe that it might be of value to try this approach, and as right now I seem to be tolerating the 140mg dose [down from 280mg], could we try one or more such supplement, while at the same time reducing my dose to 70mg?
—NB: You do NOT need to provide any answers during this appointment. However, I would appreciate a response, if possible, within the next two weeks. Thank you!
*** “In checking for the ability to kill the cancer cells it was found that Reishi [G. lucidum] caused the destruction of the myeloma (U937 cells, RPM18226 cells), leukemia (HL-60), and lymphoma (Blin-1 cells) cells assessed for this from 21% to 92%. — Reishi Mushroom causes the destruction of leukemia, lymphoma, and multiple myeloma cells —invitehealth.com/reishi-mus... — Abstract: “…”These results indicate that G. lucidum extract has a profound activity against leukemia, lymphoma and multiple myeloma cells.” — Ganoderma lucidum causes apoptosis in leukemia, lymphoma and multiple myeloma cells — pubmed.ncbi.nlm.nih.gov/164...
*** “…our results suggest that cordycepin possesses a synergistic cytotoxic effect with Cordyceps militaris-mediated apoptosis in human leukemia cells…” — Synergistic property of cordycepin in cultivated Cordyceps militaris-mediated apoptosis in human leukemia cells — doi.org/10.1016/j.phymed.20...
*** “Combined treatment with the medicinal mushroom Ganoderma lucidum and the herb Duchesnea chrysantha extracts (GDE) causes a synergistic induction of mitochondrial damage and apoptosis in HL-60 cells. GDE treatment is selectively toxic to HL-60 leukemia cells whereas no cytotoxic effect is observed in normal peripheral blood mononuclear cells.” — Enhanced induction of mitochondrial damage and apoptosis in human leukemia HL-60 cells by the Ganoderma lucidum and Duchesnea chrysantha extracts — doi.org/10.1016/j.canlet.20...
*** * “Shiitake mushrooom, Lentinulaedodes produces lentinan, a β-glucan known to suppress leukemia cell proliferation.…Treatment with cordycepin from C. militaris significantly inhibited human leukemia cell growth in a concentration-dependent manner by inducing apoptosis.…Fruiting body [of a novel edible mushroom, Pleurotustuber-regium] extract showed the strongest cytotoxicity (approximate IC50 25 μg/mL) and exerted effective anti-proliferative activity at 200 μg/mL against human acute promyelocytic leukemia cells (HL-60).…” Recent developments in mushrooms as anti-cancer therapeutics: a review, — 3 Biotech. 2012 Mar; 2(1): 1–15. Published online 2011
*** “ A…2017 study tested Artemisia extract against K562 and HL-60 human leukemia cells. This study found the Artemisia extract killed the leukemia cells of both types within 48 hours of contact. …The researchers found…Artemisia absinthium killed 75 percent of the leukemia cells, with 70 percent killed within the first 48 hours.” — Artemisia Herb Inhibits Growth of Multiple Cancers — JOURNAL OF PLANT MEDICINES | ISSN 2689-4548 | CURRENT ISSUE: VOL. 7. NO. 2, 2017
*** “It is known that RSV [resveratrol]: may exert its activity on human PBMCs in a bi-phasic/dose-dependent way; is cytotoxic to lymphoma and leukemia cancer cells since it can trigger apoptosis, autophagy or senescence…” — The Multiple Mechanisms of Cell Death Triggered by Resveratrol in Lymphoma and Leukemia, Int J Mol Sci. 2014 Mar; 15(3): 4977–4993. Published online 2014 Mar 20
*** “There is accumulating evidence that green tea extract EGCG [(-)-epigallocatechin-3-gallate] may exert a preventive or a direct anti-tumor effect in several tumor types including chronic lymphocytic leukemia (CLL).…These data suggest that EGCG exerts a pro-apoptotic effect and activates other cell killing mechanisms in CLL cells.” — Green Tea Extract EGCG Induces Apoptosis in CLL Cells and Overcomes the Supportive Effect of Primary Bone Marrow Stromal Cells Through the Regulation of PI3K/Akt Cascade and Proteasome Activity, 641. CLL - BIOLOGY AND PATHOPHYSIOLOGY, EXCLUDING THERAPY: POSTER III| NOVEMBER 16, 2012
*** “…patients with CLL benefit from curcumin due to its immunopotentiator properties resulting in protection from infectious diseases [CLL] [19]…Curcumin…also…induces micronuleation and apoptosis…Kao, et al…observed that curcumin was capable of inducing apoptosis in promyelocytic leukemia HL-60 cells at low concentrations of 3.5ug/ml.…Curcumin…is beneficial in leukemia, especially in early stages of CLL It prevents the progression of the disease, decreases CLL B-cell counts, and, also when administered together with conventional anti-cancer drugs, has synergistic actions, in addition to lowering their dose and side effects.” — Curcumin in chronic lymphocytic leukemia – A review — Asian Pacific Journal of Tropical Biomedicine, Volume 7, Issue 6, June 2017, Pages 505-512
*** “In summary, we found that H2O2 preferentially affects leukemic cells by decreasing their viability, quiescent state and clonogenic capability via the modulation of survival signaling through decreased AKT activity. From a clinical point of view, treatments based on the ROS modulation levels are a promising therapeutic tool, once the redox state-induced alterations can cause selective hematopoietic cell fate, sensitizing leukemic cells to death.” — Hydrogen peroxide (H2O2) induces leukemic but not normal hematopoietic cell death in a dose-dependent manner — Cancer Cell International volume 13, Article number: 123 (2013)
* Cancer Cell International volume 13, Article number: 123 (2013)
*** “The present findings indicate that Antho 50 [from bilberry] exhibits strong pro-apoptotic activity through redox-sensitive caspase 3 activation-related mechanism in B CLL cells involving dysregulation of the Bad/Bcl-2 pathway. This activity of Antho 50 involves the glucoside and rutinoside derivatives of delphinidin. They further suggest that Antho 50 has chemotherapeutic potential by targeting selectively B CLL cells.” — Bilberry extract (Antho 50) selectively induces redox-sensitive caspase 3-related apoptosis in chronic lymphocytic leukemia cells by targeting the Bcl-2/Bad pathway — Sci Rep. 2015; 5: 8996. Published online 2015 Mar 11.
*** “In summary, we found that H2O2 preferentially affects leukemic cells by decreasing their viability, quiescent state and clonogenic capability via the modulation of survival signaling through decreased AKT activity. From a clinical point of view, treatments based on the ROS modulation levels are a promising therapeutic tool, once the redox state-induced alterations can cause selective hematopoietic cell fate, sensitizing leukemic cells to death.” — Hydrogen peroxide (H2O2) induces leukemic but not normal hematopoietic cell death in a dose-dependent manner — Cancer Cell International volume 13, Article number: 123 (2013)
* Cancer Cell International volume 13, Article number: 123 (2013)
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Pogee
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One hugely important matter you need to use to whittle down your search results is that many of the leukaemia references are for acute, non B-cell leukaemias or at best other B-cell leukaemias. The latter might possibly be of interest, but the former references should usually be seen of low relevance, because the driver mutations (and hence what you want to inhibit) are totally different. A relevant example is the amount of cordyceps research for CLL or lymphoid cancer and myeloid cancers as covered in this post
CLL is the most common adult leukaemia/lymphoma, so look for references using CLL stem cell lines. You should also be very cautious about papers citing apoptosis in in vitro testing or in mouse models and look for human in vivo studies. That's because CLL cells do a very good job of providing themselves with stromal cell protection in the nodes, buffering them from the effects of apoptosis triggering substances.
You now have the exercise of going through your references and scoring them against the above. I expect you'll have far fewer possible options. (You can edit your post to add in a 'score' or delete poor candidates via the 'More v' below your post).
There has been some study of using natural substances to synergistically improve the efficacy of proven treatment drugs for CLL, in fact Mayo Clinic patented the use of EGCG in such a manner. In my opinion, EGCG has the best evidence by far for the use of a natural substance to hopefully slow the progression of CLL, but it has toxicological issues and typically causes what can be distressing digestive side effects, which I have experienced. Turmeric is probably the next most promising natural substance and indeed in vitro experiments (where it was established that it did not synergistically work with EGCG), looked encouraging. However, an actual clinical trial with CLL patients was rather disappointing, as is usually the case with CLL for the reasons I gave above: healthunlocked.com/cllsuppo...
The fact that Mayo Clinic haven't proceeded with further research I think shows how very effective current CLL treatment drugs already are.
As I replied to you earlier, "The challenge with the approach you are suggesting, (using a natural substance to reduce the dose of a effective treatment drug), is that you don't know the strength of the impact on CYP3A4, which naturally varies with seasonal variations in the mushrooms, curcumin, black pepper, etc, the processing, degree of freshness and so on. This is a fundamental difference between prescription medication and supplements, the degree of control of the active ingredient. This is exactly why the use of supplements and herbal remedies is not encouraged when you are on a clinical trial.
It is very important that you maintain inhibition of CLL cells from your treatment drug, because CLL cells not inhibited from multiplying can give rise to sub-clones with resistance to the treatment and if they aren't inhibited, then you aren't maintaining control of your CLL. Is it possible to reduce the consumption of substances that are known to influence the effect of CYP3A4?"
In my opinion, going down to a 70mg dose of Ibrutinib is potentially a very dangerous path. That's because the only way you can do so, is taking a 140mg tablet every other day. You can't halve a 140mg dose, because you need the enteric coating to ensure it is best absorbed into the blood stream! With the half life of Ibrutinib, you are leaving open a window for incompletely inhibited CLL cells to divide and develop resistant sub-clones.
I've been collating references to commonly suggested natural substances in my first reply to this post: healthunlocked.com/cllsuppo...
It's not very encouraging, which is not surprising, when you consider how very effective the newer clinically proven treatment are nowadays.
Thank you for the information. However, most of the enteric coating remains when the pill is cut in half, whether it's a 280 (which I have) to 140 or 140 to 70mg. By the way, they also make a 70mg pill. Question: Can you advise why the minimal area that isn't enterically coated (I'm guessing about 10-20% of the entire coating) is of such overriding importance?
Drop a pill into an acidic environment and see how rapidly the tablet dissolves from the non-enteric coated end - or just accept the manufacturer's recommendation NOT to break the pills!
When pills have an enteric coating (or come in a gel cap, which is how I had my ibrutinib), the point of these encasements I believe is so that the pill passes through the stomach and does not begin to break down/release until it enters the duodenum where it can be better absorbed and won't be swamped by stomach acid. You defeat that if you cut the pill. I myself have very much benefited from low-dose ibrutinib. But I would not go below 140 mg.
Thank you for the advice. AussieNeil said precisely the same thing. However, I think by cutting the pill in half I'm simply exposing a small percentage of the pill, while the enteric coating remains on the rest. So far, I'm not having any stomach aches or other issues related to this, so far as I can tell, but we'll see.
If the exposed part is not effective because of that exposure to acid, you will have even less effective use of the medication and have no idea how much dosage you are receiving. The effect will not necessarily be on the stomach, it will be low or no effect on your CLL.
I appreciate your comment. At least 3 people have said the same thing. My oncologist today didn't think that would be an issue; however, he apparently doesn't have the sophisticated knowledge that you all do.
Pogee, I'm not an expert but I believe it is as AussieNeil , PlanetaryKim , and cllady01 have said - by cutting the pills in half and exposing part of the insides, you could be making a difference to the amount of medication that your body is absorbing. (You may not be simply getting half the dose).
Once you've broken the seal round the pill, even if only a small area of it is exposed, stomach acid can get in and affect all of the medication inside.
I'm not sure how much of a difference this may make, but I believe the manufacturers have good reasons for putting coatings round certain pills. Have you talked this over with your doctor?
I appreciate your comment. At least 4 people have now said the same thing. My oncologist today didn't think that would be an issue; however, he apparently doesn't have the sophisticated knowledge that you all do.
Excellent post, God Sir! I recognize the vast differences between in vitro and mice-driven lab results and humans-as-guinea-pigs trials—and I will go back to the drawing board with regard to the listed drugs, supplements, etc., in my post. However, I thought, regardless of any other findings, that these were sufficiently valid as a starting point for others who might wish to engage in more advanced research. As noted, none of the data in that post represents medical advice!
I am responding to Neil's post to share my experience with EGCG. Supplements may not always be trouble free. I wrote this post below to Pogee 2 or 3 days ago but it was late in the day( U.S. time )so I suspect many did not see it. I happened to leave out that my ALC was 5000 at dx and has now plateaued for the last six mos or so at 65000, an indolent course I have been told.
I think most people when given a cancer dx, esp something like CLL and many with prostate cancer who are told to w+w, start looking and hoping for ways to affect their chances for improvement and survival. It feels maddening and counter intuitive to do nothing and wait for cancer to get worse. In my case I began the green tea extract and curcumin regimen. Those of us who tried this were hoping to find the right green tea ext. b/c that used in the original trial was not available to the public. As I worked my way up to 1400 mg a day ( 4000 mg /day is the target as I recall) nighttime urination increased to 4-5x a night. Already having yrs of prostate related sxs, this made nocturia worse. Several days in a row waking up to pee that many times is not conducive to restful sleep and overall health. I stopped green tea ext but cont to take 400mg/day of curcumin for its anti inflammatory benefit.
I am 13q, CD 38+ and borderline IVGH mutated. November will mark year 6 since dx. All the other main numbers we watch are still at the lower end of normal. For a time my neutrophils were steadily declining but they bounced back up. In the last yr I have started to develop some enlarged nodes on my trunk so I am prob now elevated to stage 1. While I experienced many a sleepless night in the first couple of yrs along with what was likely my one and only period of clinical depression in my life, I consider myself fortunate to be where I am now. Many others with CLL have a much more scary and troubling time with this illness. The newer tx's and rich, ongoing research give hope to all of us.
This forum has been a godsend. So much knowledge and support. I appreciate all that our members contribute, esp those who share their abundant knowledge, even during times when they may be going thru a tough time themselves with CLL.
Long live the memory of Chris Dwyer who gave so much to this group.
A loving and heartfelt post. I, too, feel that no matter what I might be going through, literally millions of people are so much worse off, so I need to be grateful and humbled for the blessings I have. I'm in awe of the administrators of this marvelous site, most especially AussieNeil, who devotes so much of his time, energy, knowledge, patience, and passion to and for the rest of us. I never knew or had contact with Chris Dwyer, since I'm a newbie here, but I'm happy to celebrate his good memory for those of you fortunate enough to have benefitted from his love and wisdom.
I have not heard of any doctor reducing a recommended dose of a btk inhibitor on account of any supplements. You might consider boiling down your questions to a lesser number. My doctor always took the time to answer my questions, but I was aware that he can only allocate so much time a day to one patient.
It is normal for our wbc to go up as ibrutinib flushes Cll cells from our nodes into our bloodstream. What is counter intuitive is that people who take more than a year or two to get their wbc in normal range do as well or better than those who have their wbc normalize more rapidly.
My doc did encourage me to exercise, eat well and enjoy a good glass of wine now and then. He thought green tea was okay for me too, but I should drink it because I like the taste, not because it will have any meaningful impact on my leukemia.
If you are having problems tolerating Ibrutinib, asking about trying acalabrutinib is one of the more important questions I see on your list. None of the three specialists I saw recommended any supplement for me other than folic acid for my hemolytic anemia. Good luck to you.
Thank you for your post. I'm quite sure that my oncologist won't have anything good to say about mushrooms, EGCG, herbs, and the like, as Western medicine focuses like a laser on drugs and surgery. Nonetheless, I plan to ask the questions, and to take all the time I need. I've spent many hours, literally, waiting to see one or more doctors, after he/she double booked and got backed up for other reasons. As my life is on the line, I have no compunction about holding my ground on this. At the same time, if he is less than accommodating, I've already found another, apparently marvelous, oncologist who has 234 five-star reviews out of 235 total reviews! But since she's quite distant, I'll stay with my current oncologist, if he comes through, as I truly like and respect him. Best to you!
Well I certainly wish you the best in your quest for information. You might find a doctor who is okay with one or more supplements you wish to take. I doubt you will find any top Cll specialists who agree that any combination of supplements would justify reducing the recommended dose of a Cll drug. It is not uncommon, however, to see doctors reduce a dose due to tolerance issues or because some endpoint has been reached.
I do not agree that doctors are all about medications, lasers and surgeries. We have many members in this site who have been in watch and wait with their doctors taking no treatment for many years. We even have members frustrated their doctors are not recommending treatment.
I read you loud and clear. I just came back from my doctor's visit and, true to form, he doesn't recommend any herbs. At the same time, he listened carefully, took the handouts I gave him, indicated that the last timer I presented him with information he looked it up and spoke about it, and certainly seems open to my questions, comments, and suggestions for treatment going forward. Overall, I'm most pleased with him, but also understand that all decisions are ultimately mine to make, and that I bear all responsibility for them.
Sounds like you have a good doctor and I think it speaks well of him that he takes the time to research information you provide to him. I try to keep an open mind as to supplements and such. The three specialists I have seen appear to share the view of your doctor.
With CLL, you'll do best seeing a specialist who sees lots of CLL patients. That's generally a haematologist or a haematologist/oncologist, with an oncologist who specialises in solid tumours, lowest in priority.
Thank you kindly. I've actually seen the list. My wife and I moved down to southwest Delaware, and the nearest of those recommended doctors is about 100 miles away. In addition to my current oncologist, who I like and respect, there's one about 40 miles away, who has the most marvelous reviews and who accepts new patients with coverage. So, I'm fortunate to have a fallback position. Hopefully, everyone here does, too.
So, I was also interested in reishi, and for 3 straight months all I drank was a coffee/tea/latte product containing ganoderma. The tea also contained cordyceps. Although I felt great, was sleeping better, had more energy, it was in fact boosting my immune system, which isn't necessarily a good thing.
My WBC spiked, my lymphocytes spiked, my platelets tanked and my spleen increased from 16 to 25cms. All in only 3 months. It was all of that that caused me to require treatment. Im currently doing chemo. (FCR).
Anything that boosts upper immune system, you need to be careful with as you never know what effect it will have on the different cells of your immune system when ours is a cancer that is directly related to the immune system.
That being said, once I'm cancer free, my oncologist has given the okay to use it to give my new, healthy, immune system a boost.
I'm so pleased to hear to you're cancer free! Your WBC level spiking is to be expected, first, because of the drug you were on and, second, because of the potent inducer to your liver enzyme CYP3A4 that are in ganoderma and Cordyceps. That inducer, generically, is beta glucans. This confirms my suspicion that when taking such supplements one should reduce the level of the drug they're on.
The WBC spiking, possibly due to taking those supplements, was what triggered Disneymom's need for treatment! Disneymom is on FCR, which doesn't cause a spike in WBC. That spiking usually happens on BTK and PI3K inhibitors (Ibrutinib and Idelalisib and second generation versions thereof).
Something I read back months ago when researching CLL made me quit any beta glucans. Seem to recall it was because it increased B cells, which I already have too many of, or something like this. But I'm reading here that Reishi and Cordyceps are beta glucans, right? AHCC I have wondered about, toyed with trying, which I believe is an alpha glucans. Tried to do more research on the precise immune affect from alpha glucans but have not had that much luck. Any info on the workings of either of these glucans by anyone would be appreciated.
Found this on Agaricus -- an alpha glucan. Tends to increase T Cells and decrease B --isn't that what we Bcell CLLfolks want? Here is the table (sorry it comes out so large; was more compact in original)Table 1
Antitumor effects of Agaricus blazei Murill—Preclinical studies.
In a nutshell, you would expect that B Cell Receptors (BCRs) on IGHV mutated CLL cells (M-CLL) would be randomly keyed to a broad range of stimulating antigens, with no particular preponderance with regard to selectivity to a given antigen. (Antigens are the identifying surface protein expressions of bacteria, viruses and fungi, which are recognised by a BCR, stimulating B-cell division, which would normally increase the number of maturing plasma cells that produce antibodies to label the bacteria, etc for destruction by the immune system).
Interestingly, it turns out that there are stereotyped B-cell receptors in one-third of CLL cases: ashpublications.org/blood/a... One of those stereotyped BCRs keys to β-(1,6)-glucan, from yeasts and fungi including mushrooms, which tends to imply that prior yeast/fungi exposure might predispose some of us to developing CLL and re-exposure would stimulate CLL growth. Interestingly too, beta glucan is promoted as a lymphocyte stimulant.
Here is the paper which describes "a new subset of M-CLL, expressing stereotypic BCRs highly specific for β-(1,6)-glucan, a major antigenic determinant of yeasts and filamentous fungi describe a new subset of M-CLL, expressing stereotypic BCRs highly specific for β-(1,6)-glucan, a major antigenic determinant of yeasts and filamentous fungi". pubmed.ncbi.nlm.nih.gov/232... and this post discusses it: healthunlocked.com/cllsuppo...
When Chris/CLLCanada first raised concern about this, we didn't know how frequently CLL cells were stimulated by β-(1,6)-glucan. (Beta Glucan is an essential part of fungi and yeast cell wall structures). Subsequently a paper determined that it was less than 1% of those with CLL in their particular test group, but that percentage likely varies with location/yeast/fungal exposure. Based on this research, some of us are likely to see our CLL tempo increase if we are exposed to fungi and indeed one member (DisneyMom) reported seeing their CLL take off when they took Beta Glucan. In summary, it would be wise to monitor your lymphocyte count if you decide to change your diet or take herbal supplements with beta glucans to check if you fall into the impacted group.
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