Mistletoe is a plant that grows as a parasite in various trees. It is well known as a Christmas decoration, under which lovers are kissing each other. There are various types of Mistletoe species but the name mistletoe typically refers to the Viscum album species.
Mistletoe extracts are among the most widely used in integrative cancer care treatments, at least in Europe. It has been a
successful remedy for advanced cancer since 1917 – in 2003 more than 18 million daily doses were prescribed in Germany. (Ref.) This is because of the relatively rare combination of important aspects: i.e. low cost, availability and anti-cancer potential underlined by a large amount of academic research and positive case reports in humans, some of which will be discussed below. It’s a treatment that most can afford and can be easily and fast applied. It’s safety profile is well known, since it has been used in the treatment of cancer for the past ~100 years.
The amount of academic literature on Mistletoe (Viscum album) is large (Ref.1, Ref.2), and even more impressive is the amount of positive scientific reports following its use in humans either as a stand alone therapy or in combination with chemotherapy. Some of these reports are listed in one of the sections below.
Just to be clear, like with all conventional or alternative treatments, this is not a cure-all cancer treatment. Some patients may not benefit at all from Mistletoe. But what is clear is that based on all the reports available, many patients have benefited while using it and according to scientific reports from multiple sources, some have even been cured of cancer while on Mistletoe as a stand alone treatment. Therefore, this to me is a promising treatment that can be even applied at home.
As it grows in multiple types of trees, Mistletoe contains various anti cancer substances depending on the host tree. Accordingly, there are multiple types of mistletoe solutions, each used for specific category of cancers. In addition, each type of Mistletoe solution can be found in various concentrations. Furthermore, there are various brands producing it. This variety makes it challenging for someone in need to have this subject clear as soon as possible. As a result, in this post I do not intend to get too deep into the scientific aspects, but more into creating a structured overview so that everyone can understand what may work best for what cancer type and what is the fastest route to application. Before that we will have a look, shortly, at why Mistletoe may be effective against cancer and highlight several case reports showing that indeed Mistletoe can help fight cancer.
Therefore, the purpose of this post is to put the reader on a fast track learning curve regarding the use and outcomes of Mistletoe in cancer.
Note: as discussed in the “Synergies” section below, when tumors are advanced, immune activation by Mistletoe will need to be supported by alkalizing treatments. If that is not done, in my opinion the chance for effectiveness of any immune activating therapy, including Mistletoe, will be very low.
For those who have a bit of time, here is a good YouTube movie on Mistletoe https://www.youtube.com/watch?v=d3yHlFy0g-0
Why Mistletoe may help fight cancer and for what cancer types?
Essentially, Mistletoe exhibits both direct and indirect (immune modulating) antitumor activity (Ref.) This antitumor activity is related to the Mistletoe extracts containing a number of biologically active compounds, mainly the mistletoe lectins (ML I, II, and III), viscotoxins, and other low molecular weight proteins, which exert immunomodulatry, cytotoxic, apoptotic, and antiangiogenic effects (Ref.). Mistletoe lectins stimulate secretion of a number of cytokines including IL-6, IL-12, IL-1, and TNF-α, (Ref.) and may enhance cytotoxic NK-cell activity (Ref.). In a dose-dependent manner, lectins may upregulate protein synthesis in neutrophils at low doses, while high doses resulted in neutrophil apoptosis (Ref.) This could make low dose Mistletoe treatment relevant to combine with radiotherapy since higher level neutrophils may increase chance for abscopal effects (see https://www.cancertreatmentsresearch.com/increasing-radiation-effectivness/).
It’s anti cancer activity has been observed against most tumor types. Here are a few examples, but we can always search the literature for the one we are specifically interested in:
- Fraxini extract was found to be more potent against colon cancer cells than chemotherapy drug (Ref1., Ref.2)
- Breast and gynaecological cancer (Ref.1, Ref.2, Ref.3, Ref.4)
- Merkel cell cancer (Ref.)
- Lymphoma (Ref. page 181, Ref.2, Ref.3, Ref.4)
- Laryngeal cancer (Ref.)
- Melanoma (see case reports below + Ref.)
- Glioma (Ref.)
- Cutaneous squamous cell carcinoma (Ref.)
- Acute myeloid leukaemia (Ref.)
- Pancreas cancer (Ref.)
Here is a comprehensive presentation on Mistletoe and related anti cancer mechanisms, http://www.doctoruzick.com/Mistletoe_Lecture.pdf including good references on how Mistletoe
- enhances chemotherapy anti cancer activity
- enhances radiotherapy anti cancer activity
- with a focus on why Mistletoe is highly relevant for melanoma, breast cancer, glioma and colon and colorectal cancer
Mistletoe is strongly anti-viral, so is particularly indicated in hepato-cellular carcinoma, squamous cell carcinomas,
lymphomas and leukemias.
Do we actually know anyone who benefited from Mistletoe injections?
Durable tumour responses following primary high dose induction with mistletoe extracts: Two case reports https://www.sciencedirect.com/science/article/pii/S1876382010000272 Durable tumour regression occurred in 2 patients following treatment with VAE, used in higher than generally used doses and combining different applications. Both patients had no other established cancer therapies. Further studies are required to define the strategic role of VAE and its different applications, safety and efficacy.
Successful treatment of metastatic malignant melanoma with Viscum album extract (Iscador M) https://www.ncbi.nlm.nih.gov/pubmed/17532738 The patient continued subcutaneous treatment with Iscador M after dose adaptation to 2 mg twice weekly (0.2 mL of a 10-mg vial); the treatment is still ongoing to the present. By June 2002, complete remission of the liver metastasis was diagnosed by liver ultrasound examination. There has been no local relapse so far, and the patient has been in stable condition ever since. No further metastases were discovered so far (as of May 2006).
Tumour response following high-dose intratumoural application of Viscum album on a patient with adenoid cystic carcinoma. https://www.ncbi.nlm.nih.gov/pubmed/25082867 The tumour decreased in size, softened and loosened from its surroundings. A biopsy during the course showed inflammation.
The case for mistletoe in the treatment of laryngeal cancer (Ref.) To present the case of a patient with laryngeal carcinoma who made a full recovery following mistletoe therapy, despite failing to respond to chemoradiotherapy and salvage laryngectomy. Following treatment with mistletoe extract injections after palliative radiotherapy, he recovered fully and was eventually discharged from care.
Mistletoe preparation (Viscum Fraxini-2) as palliative treatment for malignant pleural effusion: a feasibility study with comparison to bleomycin https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004388/ Overall clinical response was reported in 61.5% of the mistletoe preparation arm versus 30% in bleomycin arm.
Minor regression and long-time survival (56 months) in a patient with malignant pleural mesothelioma under Viscum album and Helleborus niger extracts-a case report. https://www.ncbi.nlm.nih.gov/pubmed/29312767 This is a rare case of an MPM patient not receiving any standard anticancer treatment; it still shows an extraordinary long survival and good performance status.
Complete remission and long-term survival of a patient with melanoma metastases treated with high-dose fever-inducing Viscum album extract: A case report. https://www.ncbi.nlm.nih.gov/pubmed/29145317 A 66-year-old MCM patient with newly diagnosed lymph node metastases opted for sole VAE treatment. VAEs were initially applied subcutaneously, and then later in exceptionally high, fever-inducing doses, both intravenously and intralesionally. The metastases shrunk over the following months, and after 2 years, all lesions had completely remitted (regional and hilar lymph nodes). The patient has been tumor free for 3.5 years at the time of publication (and for 5 years since initiation of intensified VAE treatment). Besides fever and flu-like symptoms, no side effects occurred.
Health services research of integrative oncology in palliative care of patients with advanced pancreatic cancer. https://www.ncbi.nlm.nih.gov/pubmed/27485618 Patients combining VA with chemotherapy showed longest survival.
Survival of cancer patients treated with mistletoe extract (Iscador): a systematic literature review https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804713/ Despite obvious limitations, and strong hints for a publication bias which limits the evidence found in this meta-analysis, one can not ignore the fact that studies with positive effects of VA-E on survival of cancer patients are accumulating.
Randomised and non-randomised prospective controlled cohort studies in matched-pair design for the long-term therapy of breast cancer patients with a mistletoe preparation (Iscador): a re-analysis. https://www.ncbi.nlm.nih.gov/pubmed/17182361 The re-analysis demonstrates that the effects shown in the previously published data are consistent despite using different analytic methods and different subsets. Overall, the survival of patients receiving mistletoe treatment with Iscador is longer in these studies.
Survival of glioma patients after complementary treatment with galactoside-specific lectin from mistletoe. https://www.ncbi.nlm.nih.gov/pubmed/10928154 analysis of stratified stage III/IV glioma patients demonstrated: 1. a tendency for a prolongation of relapse-free survival for patients of the treatment group (17.43 +/- 8.2 months) vs. the control group (10.45 +/- 3.9 months) 2. a statistically significant (BRESLOW p = 0.035) prolongation of the overall survival for the treatment group (20.05 +/- 3.5 months) as compared to the control group (9.90 +/- 2.1 months). These promising data warrant confirmation in a GCP-based prospectively randomized (multicenter) study, which is currently under consideration.
Durable response of cutaneous squamous cell carcinoma following high-dose peri-lesional injections of Viscum album extracts–a case report. https://www.ncbi.nlm.nih.gov/pubmed/23394841 A 78-year-old patient with histologically diagnosed CSCC refused surgical excision and was treated with peri-lesional high-dose VAE. After 10 months of treatment the CSCC had disappeared clinically. The patient has been recurrence-free for 4 years.
Favorable long-term outcome with mistletoe therapy in a patient with centroblastic-centrocytic non-Hodgkin lymphoma https://www.ncbi.nlm.nih.gov/pubmed/10605421 Treatment with an extract of mistletoe (Iscador) was initiated and has been continued to-date (12 years). Quality of life throughout ths period has remained good. Phases of uninterrupted treatment resulted in lymphoma regression (regionally complete), while cessation of treatment led to progression.
Durable Regression of Primary Cutaneous B-Cell Lymphoma Following Fever-inducing Mistletoe Treatment: Two Case Reports. https://www.ncbi.nlm.nih.gov/pubmed/24278797 The patients are in remission to date, 3.5 years after commencement of treatment. Neither patient received conventional cancer treatment during the entire observation period.
Cancer patient given two months to live in remission following mistletoe therapy http://www.deadlinenews.co.uk/2016/09/15/cancer-patient-given-two-months-live-remission-following-mistletoe-therapy/
At the reference below, is a very good overview showing statistically better outcome for patients using mistletoe for various cancer types including:
- Rectum carcinoma
- Colon carcinoma
- Stomach carcinoma
- Non–small-cell bronchogenic carcinoma
- Small cell bronchogenic carcinoma
- Breast carconoma
Reference: USE OF ISCADOR, AN EXTRACT OF EUROPEAN MISTLETOE (VISCUM ALBUM), IN CANCER TREATMENT: PROSPECTIVE NONRANDOMIZED AND RANDOMIZED MATCHED-PAIR STUDIES NESTED WITHIN A COHORT STUDY http://www.anthromed.org/UploadedDocuments/3_32.pdf
Which Mistletoe for what cancer type?
There are four major manufacturers: Abnoba, Iscador, Helixor and Iscucin. Rarely used mistletoe extracts are from Lektinol, Isorel, and Eurixor. (Ref.) The strength of the solution for injection provided by these manufactures is very different, and so the quantity used for therapy. Here is a Figure showing the typical range used by the doctors depending on the brand https://www.hindawi.com/journals/ecam/2014/724258/tab1/
There are various differences in the manufacturing proces. For example, Iscasdor is fermented, while Helixor is not.
Depending on the tree on which is growing,
- the most common mistletoe host trees were ash (fraxini), apple (mali), oak (quercus), pine (pini), and spruce (abietis)
- other host trees are maple (aceris), birch (betulae), elm (ulmi), willow (salicis), almond (amygdali), poplar (populi), hawthorn (cratagi), and linden (tiliae). (Ref.)
Apple tree mistletoe is frequently used for breast and abdominal cancer, while pine mistletoe is used for skin cancer and tumors in the nervous system (Ref.). Breast cancer is usually treated with pin mistletoe and abdominal cancer with apple mistletoe (Ref.) Below, is for example a list showing how Helixor recommends the use of mistletoe type depending on the cancer type.
Helixor A (fir tree = Abies)
For initial therapy
During chemotherapy and/or radiation
For patients with reduced general condition
For patients with allergies/atopic diseases
For patients with intolerance of other mistletoe products
For patients with autoimmune co-morbidities (non-florid!)
For the following primary tumors:
Brain tumors or metastasis
Head and neck cancer
Helixor M (apple tree = Malus)
For pronounced immune stimulation
Excepting the indications für Helixor A, the Helixor M product is particularly beneficial for:
Gynecological and gastrointestinal tumors
Breast cancer (post-menopausal)
For injection close to the tumor
Helixor P (pine tree = Pinus)
If Helixor A and M no longer have the desired effect
For the following primary tumors:
Breast cancer (pre-menopausal)
Reference for the above: http://www.helixor.com/healthcare-professionals/drugs/helixor-a-m-p/
And here is a document from Weleda addressing potential questions from patients on the therapy (Ref.).
According to private communications from a clinician:
- Iscador brand type Qu is from oak trees. The Qu type mistletoe is used by men, including all digestive tract cancers from top to bottom, all uro-genital cancers including prostate, as well as thyroid, larynx and respiratory tract cancers.
- Helixor type A (from fir trees) is used for men’s cancers as well. Helixor A is also used for children, sensitive patients
who over-react to other forms of mistletoe, for leukemia and multiple myeloma.
- Iscador type M and Helixor brand type M from apple trees (Mali is Latin for apple tree) are preferred for women.
- P type from pine trees (Pini is Latin for pine tree) are used primarily for skin, testicular, nerve, and nasopharyngeal
cancers, sarcomas, and sometimes for post-menopausal breast cancer. Use in lymphatic cancers such as B-cell
lymphoma and CLL. P type is the most potent for stimulating the bone marrow.
How to apply Mistletoe?
Typically given in a dose escalation strategy, usually 3x/week subcutaneous injections or Intravenous (IV). Sometimes even injected directly in the tumor. When subcutaneous route is chosen, it can be easily given at home.
Usually, a small dose is placed just under the skin to form a little bubble, which should provoke a red flare like an allergic hive, as the immune system reacts. The site of the injection will get red and itchy, within about 24 hours, but should not exceed 5 cm.or 2 inches in diameter, and should vanish by about 48 hours. Large, severe or persistent rashes are an indication to reduce the frequency and dosage of the medicine. The goals is to induce a mild fever of about 1C rise, which may spike in about few hours from administration.
It is further expected to see tumor progression decelerate or even stop, improved general health, and reduced pain. It is a good bone marrow stimulant in drug-induced myelosuppression and in primary marrow diseases and that should improve as well based on statements from clinicians. Some clinicians state that they observe a good response in about 50% of advanced cancers. They further state that many patients go from being disabled and terribly sick to being active and functional, and this can last from months to years, even in the face of a difficult prognosis. However, note that due to the way of action of immune modulating therapies, it is common to see some short-term increase in tumor size. This is the aspect i do not like about immuno therapies.
Note that all treatment aspects matter (manufacturer, injection frequency, dose, etc.) so it is good to learn from the successful trials and case reports, and stick to their approach.
Example of administration procedure of Iscador from a document released by a clinician:
- The “Series 0” box has seven ampoules, and one every two days is used. Usually there is no reaction to any of the doses in this set.
- If there is a reaction (red spot around the injection site and fever) to any of the last 3 ampoules in the set, then patient will only need a tiny dose in the future. Note that the reactions will vary from day to day, so we need to look at the average size of the reactions. Here is an example of a red spot triggered at the injection site by such a therapy.
- If the Series 0 was well tolerated, and no immune reactions were triggered, the next step is to give the equivalent of 1/2 ampoule of the “Spezial 5 mg” series. It is expected to see a red flare in the skin around the injection site, about 1 inch
in diameter, arising in an hour or so, peaking at 24 hours, and gone by 48 hours
- No new dose is given until the previous reaction has vanished or at least diminished to a small red dot. If the
reaction is ½ inch across or less, the next dose will be higher. If the reaction is 2 inches or more across, the next dose is
going to be lower. Large reactions take longer to clear off
- This process of increasing or reducing the dose has to be followed until the correct dose to be maintained is found – the maintenance dose is found when the red spot around injection site clears off fast enough to allow dosing the mistletoe 2 to 3 times per week
- It is very important to never give Mistletoe during a fever over 38 °C. Mistletoe therapy is continued only after the fever is down. On the other hand a rise of core body temperature of about 1°C is a sign of a good response. Other signs of immune system activation by mistletoe can include flu-like symptoms, aching, shivering, and headache.
- A pause of 2 weeks is suggested every year in the first 2 years of use, then 4 weeks off in the next 2 years, and 8 weeks break in the 5th year and beyond. If the Mistletoe stops producing a local skin reaction, it may stop controlling the cancer.
Same source discussing Helixor:
- For some special cancers such as lymphoma or sarcomas type P from pine trees is used. The P type starts with “Series
0”, but after that comes “Series 1” and next “Series 2”, both of which have escalating dosages in each box, and can go up to 20 mg. Helixor P comes in doses up to 50 mg per mL, which could be pooled together in a multidose vial if a customized dosing protocol will be used and in order to avoid waste of remaining solution taken out of the vial
- The maximum dose used is 400 mg, and the usual dose that should not be exceeded is 1mg/kg/day.
- It is believed that there is not a problem to switch from similar doses of one product to the other, like from Iscador to Helixor . The Helixor A seems to be the best tolerated, and it is the better immuno-modulator. Therefore it may be best for children, and during chemotherapy. On the other hand, Helixor P is harsher due to higher content of cytotoxic lectins.
Example of the administration procedure in the trial on Pancreatic Cancer:
- Mistletoe type: Iscador Qu, a commercially available extract of Viscum album (L.) quercus (manufacturer: Weleda AG, Arlesheim, Switzerland).
- Strategy: Mistletoe extract was given in escalating doses by subcutaneous injection three times a week. First two subcutaneous injections of 0.01 mg mistletoe extract each, followed by two of 0.1 mg, five of 1 mg, five of 2 mg, eight of 5 mg, and finally by the constant target dose of 10 mg per injection over the remaining duration of the trial. (Ref.)
This info should be enough to be able to have a quick start in understanding how Mistletoe is used. For more ideas on successful administration procedures just browse through the articles referenced above, where successful outcomes are reported following Mistletoe use.
Here is a guide on how the injections can be done at home: http://www.weledapharmacy.co.nz/sites/default/files/Patientenanwederbroschuere_D_EN.pdf
On the Iscador website you can find clinics using it to treat cancer patients. I suggest to anyone to have any new treatment first supported by a medical practitioner to make sure any unexpected reactions are addressed well.
Note: I often discussed Iscador here. This is a result of the research info I have at hand and not because Iscador would be my preferred manufacturer. My only recommendation on this line is that if I would have to buy Mistletoe now, I would probably go for one of the following brands: Abnoba, Iscador, Helixor, since these seem to be the most experienced manufacturers and their products were used in some of the positive case reports.
Given that Mistletoe treatment is a form of immuno therapy that relies heavily on immune response, I would make sure I combine this treatment with a treatment strategy focused on lowering acidity in the body (increasing pH). This can be achieved using techniques such as those discussed here: https://www.cancertreatmentsresearch.com/ph-cancer-a-top-treatment-strategy/ This is needed since low pH typically inhibits the activation of the immune cells, through mechanisms discussed elsewhere on this website. The most accessible pH stabilizing treatment is that using Basentabs (food supplements found at online shops in Europe). More intensive and fast alkalizing treatments can be accessed at various private clinics, where e.g. intravenous Natrium Bicarbonate can be used. DCA treatment may also help towards a more alkaline tumor environment.
Note: alkalinization is strongly required when the cancer patient is in advanced stage or tumors are larger.
Other immune activating supplements such as mushrooms, e.g. Coriolus Vesticolor, may also help to maximize the potential benefits of the Mistletoe therapy.
Where to buy Mistletoe?
Most of the private cancer treatment clinics will have Mistletoe available.
Alternatively, anyone can order (without prescription) the injections at German pharmacies. You can use the following page to search the product by the manufacturer (e.g. Iscador) and related prices at various pharmacies https://www.medizinfuchs.de
What are the potential side effects and safety?
In general, it’s safety profile looks very good (Ref.):
- Safety of Intravenous Application of Mistletoe (Viscum album L.) Preparations in Oncology: An Observational Study https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4052504/
- Clinical safety of combined therapy of immune checkpoint inhibitors and Viscum album L. therapy in patients with advanced or metastatic cancer https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729272/
- Efficacy and safety of mistletoe preparations (Viscum album) for patients with cancer diseases. A systematic review. https://www.ncbi.nlm.nih.gov/pubmed/19729932
- Contraindications of mistletoe therapy: tumors of the haematopoietic system , Inoperable Gehirncarcinome with the tendency of edema , thyroiditis untreated, active tuberculosis http://www.misteltherapie-stuttgart.de/html/indikationen.html
- High doses of mistletoe lectins damaged the liver in some cases; this damage was correctable. Another review of clinical trials reported adverse effects that included increased circulatory problems, thrombophlebitis, swelling of lymph nodes, and allergic reactions. http://www.cancer.gov/cancertopics/pdq/cam/mistletoe/patient/page1/AllPages/Print
- Avoid the use of mistletoe in patients with over-active thyroid glands (a condition called hyperthyroidism). Mistletoe may cause an inflammatory reaction when used in patients with untreated hyperthyroidism.
Here is a nice list on the adverse drug reactions recorded in cancer patients treated with mistletoe extracts https://www.hindawi.com/journals/ecam/2014/724258/tab2/
Note that mistletoe is in general well tolerated nut in rare cases it may trigger allergic reactions – this is why low dose has to be always tested first in each patient.
During mistletoe therapy there may very occasionally be an activation of a hidden focus of infection in the body, such
as an occult dental abcess with anaerobic bacteria. Other extremely rare occurrences are gallstones, colon infection
and regional lymph node swelling. Cachexic patients may not do as well with mistletoe, as the increase in cytokines
aggravates their metabolic wasting syndrome. In this case Cachexia should be addressed first or at the same time, using solutions such as discussed here and anti inflammatory supplements (e.g. Omega 3) and drugs (e.g. Aspirin).
There is a laboratory in Germany that can test the immune system response to mistletoe: http://www.misteltherapie-stuttgart.de/html/kosten.html
Chemosensitivity laboratories such as RGCC can also test the potential direct (non-immune) response of tumors to mistletoe.
Viscotoxins, mistletoe lectins and their isoforms in mistletoe (Viscum album L.) extracts Iscador. https://www.ncbi.nlm.nih.gov/pubmed/16927522
Phytochemical profile and therapeutic potential of Viscum album L. https://www.ncbi.nlm.nih.gov/pubmed/25813519
Adverse Drug Reactions and Expected Effects to Therapy with Subcutaneous Mistletoe Extracts (Viscum album L.) in Cancer Patients https://www.hindawi.com/journals/ecam/2014/724258/
Targeting Inflammation in Cancer-Related-Fatigue: A Rationale for Mistletoe Therapy as Supportive Care in Colorectal Cancer Patients https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133960/
Tumour response following high-dose intratumoural application of Viscum album on a patient with adenoid cystic carcinoma. https://www.ncbi.nlm.nih.gov/pubmed/25082867
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