Beta glucans

[Christine15]

Apologies if I've asked this before but has anyone taken supplements of Beta glucans to help boost their immune system? it has been recommended to us whilst my husband is on watch and wait with no medical intervention as yet. it should help fight off routine infections. It sounds like a good idea to me to help him stay as healthy as possible for as long as possible. Any thoughts?

[AussieNeil Administrator]

Hi Christine15. Beta glucans has been raised a couple of times previously per the posts below:

healthunlocked.com/cllsuppo...

healthunlocked.com/cllsuppo...

You do need to be discriminating when suggested supplements to boost immunity - particularly when the suggestion comes from other than a CLL specialist. Remember that white blood cells are what provide immunity, but for those of us with CLL, supplements that aim to boost white blood cells may actually boost our B-cell clones, which we don't want. That may be the case with Beta glucans according to the article referenced in one of the above posts. If your husband decides to give this a try, make certain that you keep his specialist informed and monitor your husband's absolute lymphocyte count (ALC) closely for any trend changes.

Neil

[Christine15 in reply to AussieNeil]

Thanks AussieNeil. Lots to read and digest and we will do so before making a decision. My husband is back from the Doctor with antibiotics for yet another insect bite that had become badly infected. He 's been told to go to A&E for intravenous antibiotics if it gets worse. I think we need to invest in some super duper insect repellent as opposed to taking beta glucans willy nilly!!

Thanks again for an informed promt reply - it sometimes feels like a very scary lonely place to be and this forum can be a comforting lifeline.

[vepiskop]

Dear Christine,

I have been taking wellmune (beta glucan micromolecularised) since I was diagnosed Feb 2009. Dec 2009 I started having a permanent cold. Then I started 250mg Wellmune + 1000units vitamine D2, in Feb 2010 and I never fell ill again until today. The levels of CLL cells were steadily going up before and after I started taking Wellmune. My GP and my haematologist were happy for me to keep taking Wellmune.

I do not believe the references given by AussieNeil. The published papers do not mention whether you will progress faster if you are taking Wellmune. In addition, the number of CLL cells in the blood are not directly relevant with disease progression. Nobody took wellmune and progressed. Some patients have high numbers 200 (x 10 to 9) and their disease has not progressed and some others have 50 and need treatment. Bottom line, I highly recommend beta glucans, but be careful to take wellmune because it is the only one that is broken down to be easily absorbed, all others in the market are not effective. Good luck.

[AussieNeil Administrator in reply to vepiskop]

Vepiskop, I'm pleased that Beta glucan is working for you. Unfortunately, with CLL varying so much between individuals, what works for you may or may not work for others. Anyone deciding to try taking Beta glucan needs to know that in some individuals, it can drive the proliferation of their CLL. As the abstract from the reference I cited in my reply above states:

"In this study, we 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. β-(1,6)-glucan binding depended on both the stereotypic Ig heavy and light chains, as well as on a distinct amino acid in the IGHV-CDR3. Reversion of IGHV mutations to germline configuration reduced the affinity for β-(1,6)-glucan, indicating that these BCRs are indeed affinity-selected for their cognate antigen. Moreover, CLL cells expressing these stereotypic receptors proliferate in response to β-(1,6)-glucan (my emphasis)."

That clearly tells me that for individuals with the mutated form of B-CLL (the M-CLL mentioned above and that's most of us), there's a not insignificant subset (a portion of the over 30% based on their expression of stereotypic B cell receptors), where the mutated B-CLL clone is keyed to Beta glucan and that these individuals will see a proliferation of their CLL when exposed to it.

Therefore some of us with CLL should not take the Wellmune supplement containing Beta glucan, for the simple reason that we happen to have stereotypic BCRs on our cancerous B-cells keyed to Beta glucan, which is a common antigen from yeasts and fungi. Where those proliferating B-cells concentrate will again vary for each individual, the peripheral blood in some, lymph nodes, the spleen or bone marrow in others. Most of us won't see a change in our CLL and may benefit from taking Beta glucan. The problem is that we can't be sure which camp we fall in, as the testing required is only available in research laboratories.

You are quite correct in stating "the number of CLL cells in the blood are not directly relevant with disease progression" and that's the worry. How does an individual know whether they are increasing their tumour burden in their bone marrow or internal nodes without a bone marrow biopsy or CT scan respectively?

You've also stated "Nobody took wellmune and progressed." I'm sure our members would love to have more information on that study, including the reference, so that they can get a better feel for the degree of risk/reward involved.

Thanks,

Neil

[Hidden in reply to AussieNeil]

AussieNeil- Again, many thanks for your many helpful posts! I just posted a note today March 6, 2018- asking whether I should stop eating mushrooms because of their beta glucan content. I do not take beta glucan supplements, only eat mushrooms a couple of times a week. This subject is very confusing! By the way, I am unmutated, so perhaps beta glucan works differently with mutated versus unmutated people? Should I stop eating mushrooms? I appreciate your depth of knowledge on this subject and would really appreciate anything you can share! Wishing you good health, my friend. -G

[AussieNeil Administrator in reply to Hidden]

You would need B Cell Receptors specific to beta glucans antigens to have your CLL grow in response to mushrooms, ie hypermutated CLL.

I would recommend monitoring your ALC if you are concerned about the impact of any changes in your diet or supplement intake.

Neil

[vepiskop]

Dear Neil,

You are right that not everybody is the same. So let people try. It is unfair to discourage others due to your personal experience. Be more open. Your case is not a common one.

You seem capable to understand scientific concepts and this is why I will try to argue with you that antigen specificity is interesting but it is not the cause of CLL. The CLL cancer stem cells that give rise to B-cells that are CLL (B-CLL) are in the bone marrow and do not express BCR.

It is true that the specific antigenic response of normal B-Cells is vast but in CLL patients there is abnormally low antigenic variation of B-CLL cells. The repertoire of B-CLL cells has been show to be common between different patients and specific against viral antigens (from latent viral infections) or fragments of cell debris that normally exist in the blood stream or even cases with auto stimulation (constitutive) stimulation of BCR against BCR (Nature 489, 309–312 (13 September 2012). In the periphery (spleen and lymph nodes) BCR antigen recognition on normal B and CLL cells causes proliferation of a selected population of BCRs against specific the antigen (in healthy individuals this is agains an invading infection agent). The type of the antigen may help the B-CLL cells proliferate in the periphery but this does not cause the disease. Even if you take the antigens away, B-CLL cells will find something else ( a different antigen) to stimulate their proliferation.

The clonal amplification of the cancer stem cells is what causes the disease or makes the disease more aggressive. I have to remind you that the CLL cancer stem cells that produce the B-CLL cells are part of the bone marrow and do not express BCR. They are not amplified by BRC signalling. This is why Ibrutinib or Idelalicib which block BCR signalling cannot cure CLL.

Normal B-cells do not really proliferate in the bone but go to the periphery (lymph nodes and spleen), where they mature, and are selected upon their antigen specificity and proliferate. CLL disease progression occurs because the B-CLL cells infiltrate or amplify abnormally within the bone and suppress normal bone marrow stem cell proliferation and function (i.e. production of all haematopoetic lineages including the normal B-cells to fight infection). What makes the B-CLL cells to infiltrate the bone is unknown. It is not the number of circulating B-CLL cells, because the B-CLL number and disease progression do not correlate. Something else causes the bone marrow infiltration and the expansion of B-CLL cells within the bone . In fact one branch of the ICICLLE clinical trial with ibrutinib is designed to address whether the B-CLL cells infiltrate the bone from the periphery or they actually proliferate within the bone.

It is true that BCR signalling is responsible for B-CLL cells trapped/or even proliferating in the bone, because Ibrutinib which blocks BRC signalling, flushes the B-CLL cells out of the bone (as well as from the lymph nodes and spleen). This removal of B-CLL cells from the bone is the mechanism by which Ibrutinib treatment is so effective.

The CLL stem cells no doubt remain untouched by ibrutinib.

In conclusion, beta glucans can do more good than harm, and therefore, one should try them if they are in danger of severe infections.

I hope this helps.

Vepiskop

[AussieNeil Administrator in reply to vepiskop]

G'day vepiskop.

Thanks for your reply, which unfortunately doesn't address the issue of whether for some of us with CLL, Beta glucans may cause a proliferation of mutated CLL clones that have BCRs keyed to Beta glucans. The vexing problem of current treatments for CLL not being able to eliminate progenitor stem cells in the bone marrow is not relevant. Clonal B-cells contain a nucleus and will proliferate within a protective environment under the appropriate stimulus, which for some of us, is exposure to the antigen to which the BCR has become keyed in the IGHV mutation process.

In one place I worked we had a slogan - "In God we trust. Everyone else must bring data". I'm sure that our members fighting a battle with low immunity would welcome references from you that will enable them better assess their likely risk of attempting to boost their impaired immunity by taking Beta glucans without also risking boosting their clonal B-cell tumour burden.

Thanks,

Neil

[Hidden]

Hi Vepiskop

As you are arguing the case for wellmune beta glucan specifically, please provide the scientific study paper, supporting your assertation. Can do is not will do, certainly not in all cases.

I am not of a technical member, and I like to print off the scientifically proved facts and studies including trials, to read and understand at my leisure so look forward to reading the studies from which your post has been taken.

Although I am sure you did not mean it that way, your post comes across as slightly pompous, not what we are used to on this site where we support and encourage each other, as we have been supported and kept informed by the administrators and volunteers since this site started.

I hope you are having a good day, be as well as you can be.

Bubnjay

[vepiskop]

Dear all,

I am an expert in the field of signalling and cancer and I could write a review with all the relevant literature.

For the time being here is a review that you can download and read.

Molecular pathogenesis of chronic lymphocytic leukemia.

Gaidano G, Foà R, Dalla-Favera R.

J Clin Invest. 2012 Oct 1;122(10):3432-8. doi: 10.1172/JCI64101. Epub 2012 Oct 1. Review.

I was trying to translate some concepts for you, from several published paper but you seemed to have musudnertood me.

The absolute number of CLL cells in the blood is not associated with disease progression. This is by now a fact in CLL practice not just a note in a publication.

High proliferation rate of CLL cells > double in a year,again it is not a sign of progression but one of the bad prognostic markers.

This high rate of proliferation has not been shown to depend on specific antigens and BCR signalling but with additional gene mutations.

If you are afraid of enhancing proliferation of CLL cells by taking beta glucans, you may follow it and stop it if you see it has been increased.

But if you take it and helps you stay away from infections it would be a great help. Here I speak from personal experience.

I hope this helps.

vepiskop

[AussieNeil Administrator in reply to vepiskop]

Thanks for that reference on the causes of CLL, which can be found here:

ncbi.nlm.nih.gov/pmc/articl...

You are quite correct in stating that "The absolute number of CLL cells in the blood is not associated with disease progression." This is covered in the pinned post How high can you go? (And what does it matter?):

healthunlocked.com/cllsuppo...

However, high proliferation rate of CLL cells IS a trigger for treatment.

From Chronic lymphocytic leukemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

B. Eichhorst1 et al:

annonc.oxfordjournals.org/c...

Treatment Indications

Treatment should only be given to patients with active, symptomatic disease. The following conditions define active from lymphadenopathy, splenomegaly or hepatomegaly, lymphocyte doubling time of <6 months (only in patients with >30 000 lymphoyctes/ul) (my emphasis) as well as autoimmune anemia and/or thrombocytopenia poorly responsive to conventional therapy disease: significant B-symptoms, cytopenias not caused by autoimmune phenomena and symptoms or complications.

The lymphocyte doubling time guideline to commence treatment is found in similar publications for other countries.

Our Members generally either already have CLL or care with someone with CLL and thus are interested in whether/when they will need treatment and if so, what treatment will work best for them.

As you say, "If you are afraid of enhancing proliferation of CLL cells by taking beta glucans, you may follow it and stop it if you see it has been increased." Given the above guidelines on when to commence treatment for CLL, any member deciding to try Beta glucans in an attempt to improve their immunity would be well advised to inform their medical team and carefully monitor their ALC.

They may also be interested in reading this research study, carried out by the University of Southhampton, which was funded by Biothera/Wellmune:

Yeast-Derived 1,3/1,6 Glucopolysaccharide to Prevent Upper Respiratory Tract Infection and Modulate Circulating Cytokines and Chemokines in Older Adults

Fuller RJ et al

biotherapharma.com/healthca...

Note the Conclusions:

Wellmune demonstrated a non-significant trend towards preventing URTI in older adults in this pilot study. Symptom severity and duration were not different. Wellmune may modulate interferon gamma and MIG following LPS stimulation. Larger studies seem warranted to determine benefit in URTI prevention.

The study was not on immune compromised/CLL patients, but included older adults which overlaps well with the typical CLL patient age. I can't find the study in any peer reviewed journals, but it does appear on Wellmune and Biothera websites.

Neil

[Cllcanada Top Poster CURE Hero]

Look forward to your review... vepiskop

Until then...

nature.com/bcj/journal/v3/n...

[Hidden in reply to Cllcanada]

Thank you all, looks like I have lots of reading to do!

Do like the simplicity of your link Chris.

Bubnjay