A review of what natural compounds, alternative therapies and alternative treatments might help fight the different types of lymphoma; Research Review.
With a post-Covid 'boom’ in Lymphoma cases, many new patients are experiencing a whirlwind of emotion and confusion and simply want to know what they can do to help themselves and understand better how they might resolve the cancer without resorting solely to all the severe treatments on offer.
Here’s a review of some of the research that just might help your understanding (writes Chris Woollams, a founder of CANCERactive and former Oxford University Biochemist.)
i) What is Lymphoma?
The first thing to say is that there are quite a number of different forms of lymphoma and they don't always derive from the same causes, or interact with drugs in the same way. They are heterogeneous.
Lymphoma is a disease of the lymph system. B-lymphocytes, which are made in the bone marrow, normally respond to an infection by becoming a plasma cell, which then becomes a protein called an antibody (an immunoglobulin). Very occasionally, a Lymphoma may be due to T-cells not B-cells.
As you will see on our Personal Prescription feedback 'wall', I have helped Mustafe in Liverpool get into total remission with his Follicular Lymphoma over a year ago now. The things I did, now I have looked into this further, seem to have been spot on and included metformin, berberine, butyrate, artemisinin, magnesium, honokiol and dandelion, turmeric, green tea and raw cheese.
ii) There are two parts to the immune system
I should explain this. You are born with an Innate Immune System. This is primitive and contains T-lymphocytes that attack any bad guy entering the body. If they lose the fight, dendritic cells come along, pick up a piece of the bad guy and hand it on a plate to the B-lymphocytes. They react specifically to it and create proteins called antibodies, which are like jigsaw pieces and fit the attacker (be it a pathogen, a virus or a toxin) exactly and neutralise it. This is the Adaptive Immune System in action - built in response to infection throughout your life.
T-cells or T-lymphocytes are made in the bone marrow from stem cells and mature in the thymus. There are a number of different types. They tend to operate within cells and protect us from infection.
B cells or B-lymphocytes are also made in the bone marrow from stem cells. They operate outside cells. B-lymphocytes also secrete cytokines, which are chemical messages that can't enter the cells but can direct hormones and other factors to launch an immune attack.
T- and B-lymphocytes are termed white, or immune, blood cells. The bone marrow is part of the lymphatic system, which also includes the lymph nodes (or lymph glands), spleen and thymus.
When people have chemotherapy, their white immune cells take a big hit, exposing the patient to infection because white cells protect you from infection. This is why you are given antivirals and antibiotics. They don't always work! We have natural ones that work better.
iii) Lymphoma causes
Older people develop more, males develop more, and it is more common in developed countries. Lymphoma may run in families. Factors that increase the risk of lymphoma include -
a) Environmental toxins (e.g. from your workplace (printing inks, dry cleaning compounds, or herbicides like Round-Up, solvents such as acetone, benzene, toluene, xylene, turpentine, and various alcohols have been linked to lymphoma.). I've helped firemen, aero-industry, RAF pilots, farmers and oil platform workers.
See - Cancer in the workplace
See - Pesticides and cancer
b) Toxins you ingest such as paracetamol, drugs (like Cytosporin A), drugs for Rheumatoid Arthritis, insecticides such as DDT and Lindane, and aspartame.
See, research article on aspartame and increased risk of lymphoma.
c) Toxins you get from infections such as parasites (food poisoning), Helicobacter pylori, pathogens (e.g. E coli, Campylobacter, Coxiella), yeasts and even viruses such as HIV. There's a link between lymphoma and Epstein-Barr, and Hepatitis C. (It is thought the body may over protect itself and make too many B-cells, which do not immature.)
See - Bacterial Infections and lymphoma (1).
d) People with poor immune systems or people with autoimmune disease develop more lymphoma. In the case of Rheumatoid Arthritis, this autoimmune disease seems to increase the activity of the B-lymphocytes and changes the way they react to viruses such as EBV.
See - RA and lymphoma (2).
Comment -
* EBV is a member of the human herpesvirus family (Herpes 1, 8 - cold sores - and HPV are others). Where young people are infected, they are often asymptomatic. Research (3) shows that EBV has been linked to several forms of Lymphoma, and its presence is linked to higher rates of relapse. Its presence is highest in Hodgkin's lymphoma at about one third of patients, But the lowest link is with Follicular Lymphoma.
The virus is a potent lymphotropic agent capable of transforming B-cells in vitro into a state of continuous proliferation called ‘immortalisation’.
"Among other subtypes, a potential association with EBV was found in follicular lymphomas (2%), chronic lymphocytic leukaemia (CLL) (5%), lymphoplasmacytic lymphomas (11%), and (4%) marginal zone lymphomas".
* Helicobacter pylori, Chlamydia psittaci, Coxiella burnetii, Borrelia burgdorferi (Lyme disease) and Campylobacter jejuni have been identified (4) as present in cases of Lymphoma.
* Diabetes and poor sugar control are associated in research (5) with an increased risk of Lymphoma
* High cholesterol is not helpful either - in fact, cholesterol starvation kills lymphoma cells according to research from NorthWestern Medical School, Chicago (6).
iv) The Bone Marrow Microenvironment
First, you need to know that Stem Cells were the blob of cells that first grew when you were an embryo. From your stem cells all body cells 'differentiate' - liver, eyes, brain etc. Some stem cells get 'stuck' in their rapidly dividing form, usually under the influence of oestrogen - however, research suggests it is possible that, for example, EBV can do this too. These can become Cancer Stem Cells at the heart of a cancer. No conventional drug kills them and they generate rapidly dividing irregular B-lymphocytes. They are therefore cells that can lead to recurrence.
Bone Marrow Microenvironment - The understanding of this is in its infancy. Much of the research on PubMed is in the past 2 years! The bone marrow has its own microbiome. Bone Marrow Health, Bone Marrow fat and stem cells, which are formed in the marrow and go onto make osteoclasts, osteoblasts, T-cells, B-cells and others, are all intertwined.
Stem cells and B-cell progenitors are crucial to your health. They both exist in the bone marrow and ensure new healthy white cells are made. When B-cell lymphoma occurs, it seems that the stem cells are less likely to make fully formed, or mature, B-cells (7).
Marrow lipids (fats) are essential to the health of your bone marrow and there is a high turnover of fats in the bone marrow (8).
In one study, 'powering up' the adipocytes powered up the bone marrow lipid content and generated healthier blood cells. How did the researchers power up the Bone Marrow? The researchers gave people Metformin - ordinarily this diabetes drug is used to cut blood sugar. It does it by affecting factors in the liver and microbiome. In this research (9) Metformin unexpectedly changed the bone marrow lipid profile.
In another study (10), the health of the bone marrow was linked to the health of lymphocytes and vice versa. This same research review contains a long list of research papers on the subject.
v) The Role of the Gut microbiome
Not surprisingly, there are several research studies showing that your gut microbiome can affect your bone marrow microenvironment (For example, 11). Be clear; not just the 'bad' pathogens (parasites, bacteria, viruses) but the commensal (good) bacteria in the gut microbiome too.
Other studies, (for example, 12) show that damage to the gut microbiome by drugs and antibiotics (and food poisoning etc.) can CAUSE blood and lymph cancers (obviously by affecting the bone marrow microenvironment).
In 2015 there was a review by UCLA experts on how pathogens in the microbiome of the gut could cause B-cell lymphomagenesis. (13). The bottom line from these researchers was that pathogens can directly interact with immune cells causing oxidative stress, and with epithelial cells causing increased Reactive Oxygen Species (bad) and inhibition of NF-κB. Oxidative stress (also bad) is well understood to cause message damage in copies from your DNA and lead to carcinogenesis. For information, we know that Melatonin and Glutathione (the two biggest antioxidants you make yourself) neutralise ROS and Free Radicals in the cellular microenvironment. We have covered this several times on the CANCERactive Website.
Gut bacteria alone can cause an immune response to a pathogen and change the lymphocytes. The researchers made the point that the family Lactobacillus (250 family members or strains) seems to be significantly protective in this change.
Loss of good bacteria, gain of 'bad', is a driving force in all cancer.
Research shows that the presence of bacterium, L. johnsonii greatly reduces lymphoma risk (14). If you have lymphoma, you've probably lost it. We can replenish it naturally (not from most probiotics though - it is in none that I could find). We do it by replenishing the microbiome using unpasteurised goats' cheese.
Stress. Cancer research believes there is no link between stress and cancer - that's rubbish. Stress can increase your blood sugar levels, cause the production of Cortisol and Adrenaline which greatly increase inflammation throughout the body; and thirdly stress causes a significant decrease in commensal (good) bacterial levels in the gut and this affects cancer in cells throughout the body. (See, for example our CANCERactive review on stress and cancer),
vi) Conventional Lymphoma Treatment
Standard practice in Lymphoma is to try drug combinations to get the patient into remission.
The drugs used, until recently, were typically R-CHOP or the combo, Rituximab and Bendamustine, and now Obinutuzumab (Gazyva - a monoclonal antibody) and Bendamustine (an alkylating agent)
Most usually Rituximab will be used first. After remission ends Obinutuzumab is given on its own, then with Bendamustine. Others used are Ibrutinib and even standard chemotherapy agent cyclophosphamide. It all depends on the type of lymphoma.
The medics also add Dexamethasone or Prednisone, Paracetamol and Chlorphenamine to the mix. Dexamethasone? There are many claims that this steroid is an anti-cancer agent. It is not really. Worse, research shows a side-effect is that Dexamethasone significantly increases blood sugar.
Plus the usual antifungals (Fluconazole), antivirals (Aciclovir) and antibacterials (CoTrimoxazole) - not as good as Oregano, Artemisinin and Pau d'arco, but hey - and a couple of drugs to stop you being sick like Ondansetron and Domperidone (ginger works very well). These may impair your reactions and give you brain-fog. Usually people are warned not to drive.
Remission can last from months to up to 6 years and possibly more. If remission ends, some Hospitals use a Stem Cell Transplant, also called a Bone Marrow Transplant (15). This is particularly the case if remission ends early (16).
The SCT procedure is typically - first kill off all white B-cells with high dose drugs (usually 2 drugs and 4 rounds), and then give you a stem cell transplant (either from your own pre-collected bone marrow cells or from a matching donor.
Importantly, we know from research (17) that the stronger your microbiome, the more successful the SCT.
Other treatments are growing in usage - CAR-T treatments and companies like Transgene and looking at dendritic cell therapies and immunotherapies. Drugs such as pembrolizumab (Keytruda) work to boost the immune response against cancer cells.
Pembrolizumab can be used to treat primary mediastinal large B-cell lymphoma (PMBCL) that has not responded to or has come back after other therapies.
vii) Lymphoma info.
* See our Overview on Lymphoma, HERE
* See our Latest News and research on lymphoma, HERE - when anything new comes up that you could use, we add it.
viii) Can Natural Compounds help treat lymphoma? A review of available research.
a) There is great interest in Natural Compounds, because the drugs can be so harsh.
b) Moreover, I am really interested by the fact that this cancer may well be caused by microbiome problems and particularly infections. And, of course, the harsh drug treatments make the microbiome even worse.
c) We know some natural compounds have been shown in research to help fight lymphoma. Here, I have tried to find out what actual research exists and how good it is.
i) Fucoidan and lymphoma
* Fucoidan Overall - https://cancerci.biomedcentral.com/articles/10.1186/s12935-020-01233-8
* Fucoidan and diffuse large cell lymphoma - https://pubmed.ncbi.nlm.nih.gov/26358321/
* Fucoidan and Burkitt's Lymphoma - https://www.cancerandfucoidan.com/fucoidan-effect-on-hs-sultan-cells-burkitt-lymphoma-cells/
ii) Berberine and lymphoma
* Berberine and diffuse large B cell lymphoma - https://pubmed.ncbi.nlm.nih.gov/33930347/
* Berberine and B-cell Lymphocytic leukemia - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536443/
iii) Honokiol and lymphoma
* Honokiol: considerable influence against lymph cells (Raji) - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536443/
* Honokiol - dose dependent against Lymphoma - https://ashpublications.org/blood/article/114/22/4788/64061/Inhibitory-Effects-of-Liposomal-Honokiol-On-the
iv) Feverfew (parthenolide) and lymphoma
* Chronic Lymphoblastic Leukemia - https://oncdata.com/news/parthenolide-a-flowering-plant-compound-could-fight-cll
v) Devil's Claw and lymphoma
* Devil's Claw, Essiac and follicular lymphoma - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722058/
vi) Vitamin D and lymphoma
* Good levels of vitamin D needed to fight Follicular lymphoma - https://www.cancernetwork.com/view/vitamin-d-levels-may-be-linked-follicular-lymphoma-outcomes
* And - https://pubmed.ncbi.nlm.nih.gov/25823738/
vii) Turmeric and lymphoma
* Anticancer effect of Turmeric on B-cell Lymphoma - https://pubmed.ncbi.nlm.nih.gov/16196288/
* Cellular foundation of curcumin-induced apoptosis in follicular lymphoma cell lines - https://www.exphem.org/article/S0301-472X(05)00581-3/fulltext
* Turmeric and ECGC induce Complete remission in FL - https://www.ffhdj.com/index.php/ffhd/article/view/108
viii) Resveratrol and lymphoma
* Resveratrol induces apoptosis in transformed follicular lymphoma - https://www.spandidos-publications.com/10.3892/ijo.29.6.1561/download
ix) Genistein and lymphoma
* Genistein sensitizes Diffuse Large Cell Lymphoma to CHOP - https://pubmed.ncbi.nlm.nih.gov/14707277/
* Genistein reduces NF-κB in T-lymphoma cells via a caspase-mediated cleavage of IκBα - https://www.sciencedirect.com/science/article/abs/pii/S0006295203004155
* Inverse association between soy intake and non-Hodgkin lymphoma risk among women: a case–control study in Japan - https://www.annalsofoncology.org/article/S0923-7534(19)34633-2/fulltext
x) Quercetin and lymphoma
* Quercetin as a Novel Therapeutic Approach for Lymphoma - https://www.hindawi.com/journals/omcl/2021/3157867/
* The potential anti-cancer effects of quercetin on blood, prostate and lung cancers: An update - https://www.frontiersin.org/articles/10.3389/fimmu.2023.1077531/full#:~:text=Also%2C%20in%20combination%20with%20the,an%20aggressive%20B%20cell%20lymphoma.
xi) Melatonin and lymphoma
* Blood and lymph cancers, chemotherapy aid - https://www.eurekalert.org/news-releases/844487
* Melatonin inhibits cell proliferation and induces caspase activation and apoptosis - https://pubmed.ncbi.nlm.nih.gov/22582944/
* Therapeutic potentials of melatonin in the treatment of lymphoma: A review of current evidence - https://pubmed.ncbi.nlm.nih.gov/35384044/
xii) Thiamine and lymphoma
* B-cell lymphoma, thiamine deficiency, and lactic acidosis - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242120/
xiii) Black Cumin Seed oil (thymoquinone) and lymphoma
* Thymoquinone a new treatment option for Follicular Lymphoma - "Since TQ has apoptosis inducing potential involving cell cycle arrest and upregulation of p53 followed by downregulation of NF-kB, bcl-2 and activation of Caspase-3,-9 pathways thus it is becoming increasingly clear that it offers a new treatment option for Follicular Lymphoma." - https://jhoonline.biomedcentral.com/articles/10.1186/1756-8722-2-50
* Apoptotic and Non-Apoptotic Modalities of Thymoquinone-Induced Lymphoma Cell Death - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304872/
xiv) Aspirin and lymphoma
* Inverse relationship between aspirin and NHL - https://academic.oup.com/jnci/article/96/4/305/2606712?login=false
xv) Dandelion and lymphoma -
* Dandelion reduces chemo-resistance in Lymphoma cells - https://scholar.uwindsor.ca/uwilldiscover/2017/session1/2/
NB. Chlorella, wheatgrass, selenium, broccoli, celery and zeolite are all helpful in removing environmental toxins. Of these, there is specific research on lymphoma for
xvi) Selenium and lymphoma
* Selenium plasma concentration predicted for response to therapy, and long-term survival in patients with aggressive non-Hodgkin's lymphoma (NHL) - https://ascopubs.org/doi/full/10.1200/JCO.2004.99.240
And …
* The impact of selenium on regulatory T cell frequency and immune checkpoint receptor expression in patients with diffuse large B cell lymphoma - https://link.springer.com/article/10.1007/s00262-021-02889-5
xvii) Cannabis and lymphoma
* Cannabinoid Receptor 1 has been identified as a predominant feature of Hodgkin's lymphoma cells and could be a potential target. - https://pubmed.ncbi.nlm.nih.gov/24349109/
xviii) Carotenoids and lymphoma
* There is a significant inverse dose-response relationship between alpha-carotene intake and NHL risk (13% lower risk per 1000 μg/day increment of intake). A meta-analysis found that higher intakes of alpha-carotene and beta-carotene such as lycopene and carrots, and lutein/zeaxanthin might well protect against NHL development - https://pubmed.ncbi.nlm.nih.gov/28011986/
xx) Hypusine (lysine) and lymphoma
* Hypusine (also called lysine) is a very uncommon amino acid. It is found in bodies containing a nucleus (eukaryotes). In humans it is bound in a compound eIF-5A.hypusine-modified. Researchers from the Moffat Cancer Institute found that eIF5A is critical to the development of lymphomas that are regulated by MYC, which is almost all lymphoma. See -https://medicalxpress.com/news/2023-04-pathway-critical-lymphoma.html
Natural compounds and lymphoma - The bottom line
Several natural compounds are moderately interesting, but the research has often been done on just one form of lymphoma.
I'd be seriously looking at honokiol, berberine, selenium, maybe lysine and the top cancer stem cell killers - Turmeric with EGCG, Resveratrol and Genistein.
I'd also be wanting to replace L johnsonii, and looking into Metformin, and whether or not I had an infection such as EBV or Helicobacter pylori.
*****
References
1. https://www.mdpi.com/1422-0067/22/14/7372/html
2. https://www.webmd.com/rheumatoid-arthritis/features/the-link-between-rheumatoid-arthritis-and-lymphoma
3. EBV and Lymphoma - https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00404-7/fulltext
4. Pathogens and Lymphoma - https://pubmed.ncbi.nlm.nih.gov/32412856/
5. Diabetes and lymphoma - https://diabetesjournals.org/care/article/31/12/2391/24982/Diabetes-and-Risk-of-Non-Hodgkin-s-LymphomaA-meta
6. https://news.northwestern.edu/stories/2021/01/cholesterol-starvation-kills-lymphoma-cells/
7. https://pubmed.ncbi.nlm.nih.gov/35565219/
8. https://pubmed.ncbi.nlm.nih.gov/31668874/
9. https://www.sciencedaily.com/releases/2017/10/171016122159.htm
10. https://www.sciencedirect.com/science/article/pii/S1040842821000779
11. https://www.jci.org/articles/view/128521
12. https://www.sciencedirect.com/science/article/pii/S1040842821000779
13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047521/
14. https://www.canceractive.com/article/gut-bacterium%20reduces%20lymphoma%20risk
15. https://pubmed.ncbi.nlm.nih.gov/29452664/
16. https://pubmed.ncbi.nlm.nih.gov/29605716/
17. https://www.cancer.gov/news-events/cancer-currents-blog/2020/microbiome-health-survival-stem-cell-transplant
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