Mistletoe – immunomodulatory effect in cancer patients for improving the quality of life

ABSTRACT: Cancer is one of the distressing diseases in the world, affecting the patient’s general well-being and reducing the patient’s life expectancy. To combat this, Dr Rudolf Steiner discovered European Mistletoe (Viscum album) is useful in treating cancer patients. As a Homoeopathic practitioner, it is our obligation to improve people’s quality of life, hence Mistletoe can be used as a supportive therapy in our practice. This article demonstrates the action and effect of Mistletoe in cancer patients, demonstrating that benefit in the sense of increasing survival rates and improving patient outcomes.

KEYWORDS: Mistletoe, Viscum album, cancer, immunomodulatory effect, homoeopathy.

ABBREVIATIONS: United States (U.S.), Food and Drug Administration (FDA), reactive oxygen species (ROS), tumour necrosis factor (TNF), nitric oxide (NO)

INTRODUCTION:

Cancer is one of the world’s most challenging diseases to treat. The World Health Organization forecasts about 14.1 million new cancer diagnoses worldwide in 2012, with annual cancer deaths expected to rise to 12.6 million by 2030 ^[1]. However, it surpassed that figure in 2020 by over 10 million deaths, or nearly one in every six deaths, making it the leading cause of mortality worldwide ^[2]. For more than 50 years, plant extract preparations of European Mistletoe (Viscum album L.) have been studied as supportive cancer treatment in clinical trials, mainly in Western Europe ^[3]. The goal of homoeopathic practitioners in treating cancer is to boost immunity, reduce pain, and improve the quality of life by homoeopathic medicines with Viscum album ^[4]. This is a humble effort by the author to highlight the action of Mistletoe (Viscum album) in the treatment of cancer.

CANCER:

Cancer is the conditions where aberrant cells proliferate uncontrollably and have the potential to invade other tissues ^[5]. The word “cancer” literally means “crab, resembles “cancer attaches to the part firmly like a crab,” ^[6]. Breast, lung, colon, rectum, and prostate cancers are the most prevalent types of cancer^[7]. The determinants of cancer are environmental and genetic factors (oncogenes and tumour- suppressor genes) ^[6]. The use of tobacco, having a high body mass index, drinking alcohol, and sedentary life style accounts for about one- third of cancer – related mortality. If discovered early and successfully treated, many tumours are curable ^[7].

HALLMARKS OF CANCER^[8]:

Image 1: Hallmarks of cancer ^[8]

INVESTIGATION IN CANCER^[8]:

Investigation is required to make a diagnosis and to design the treatment plan, including:

1. The type of tumour
2. The extend of disease, as assessed by staging and investigations
3. The general health of the patient and any co-morbidities.- assessed by Eastern cooperative oncology group performance status scale and Karnofsky performance index to assess the functional capability of the patient.

Treatment:

1. Surgery
2. Radiotherapy
3. Chemotherapy
4. Immunotherapy
5. Hormone therapy
6. Gene therapy^[9].

MISTLETOE- A HOMOEOPATHIC REMEDY:

Mistletoe is the common name for Viscum album. Viscum album is listed in the Homeopathic Pharmacopoeia of the United States, which is the officially recognized compendium for homeopathic drugs in this country. Although the U.S. Food and Drug Administration (FDA) has regulatory authority over homeopathic drugs, this authority is usually not exercised unless the drugs are formulated for injection or there is evidence of severe toxicity ^[10]. To avoid this toxicity, Mistletoe can be given in highly potentised form. Viscum album is commonly used as mother tincture in homoeopathy, as well as in lower dosages to treat high blood pressure, dizziness, and arthritis ^[10].

MISTLETOE:

Mistletoe is the obligate hemiparasitic plants of the order Santalales. They connect to a tree or shrub by a feature known as the haustorium, through which they take nutrients and water from the host plant ^[11].

European Mistletoe are waxy, white berries that are produced in clusters of two to six along with smooth-edged, oval, evergreen leaves that are borne in pairs along the woody stem. Similar to European Mistletoe, the Eastern Mistletoe of North America has longer, broader leaves and longer clusters of 10 or more berries ^[11].

HISTORY OF MISTLETOE:

The Celtic druids are attributed with the use of Mistletoe as a remedy ^[12]. Since Hippocrates time, doctors have suggested Mistletoe to treat a variety of illnesses, like arthrosis, hypertension, arteriosclerosis, diabetes, and especially epilepsy. Mistletoe leaves, berries, or stems were used to make juice or powder that was administered as a medicinal drink or used topically as a plaster or ointment. When Mistletoe’s promise as a cancer treatment was discovered in 1920, new attention was generated. Rudolf Steiner founded his medical system on the principles of anthroposophic medicine and Ita Wegman was the first medical professional to expressly use a Mistletoe extract in cancer patients ^[13]. The parasitic character of the Mistletoe plant and the parasitic invasion of the human body by cancer struck Steiner as being comparable ^[12].

ACTIVE PRINCIPLES IN MISTLETOE:

Lectins, viscotoxins, flavonoids, polysaccharides, and oligosaccharides are the active components of Mistletoe. In this, a compound of viscotoxins and lectins has a major impact on cancer cells and activates the immune system ^[14].

IMMUNOMODULATORY ROLE OF MISTLETOE LECTINS IN CYTOTOXICITY:

Lectins, which are composed of both protein and carbohydrates, can adhere to the surface of cells (such as immune system cells) and cause biochemical alterations

1. Chain-B of ML-I, also known as Viscumin, binds to neutrophils and releases superoxide radicals, which in turn cause tumour cells to die by turning into peroxide radicals (H2 O2).
2. Chain-B binding to natural killer cells causes them to generate the cytokines interleukin-23, 3 and TNF (tumour necrosis factor alpha), which cause tumour cells to be destroyed.
3. Reactive oxygen species (ROS) like nitric oxide (NO), which binds with signalling lipid on cancer cell phospholipid membrane and prevents the signal cascade pathway from continuing, are also produced by cytokines ^[14].

Viscotoxins, are a class of tiny, cysteine-rich, highly basic proteins belonging to the thionin family that are poisonous to a wide range of eukaryotic and prokaryotic organisms. Positive charges on thionins interact with phospholipids in an unintended manner to cause this toxicity. Thionins permeabilise and eliminate tumoral cells as a result of their passive incorporation into cell membranes ^[15].

IMMUNOMODULATORY ROLE OF MISTLETOE LECTINS IN APOPTOSIS ^[14]:

Image 2: Immunomodulatory effect of Mistletoe Lectin in Apoptosis

MODE OF PREPARATION:

Mistletoe plants are processed and manufacture separately based on the host trees. The preparation name indicates the host tree from which the extract is derived. Thus, the letter M stands for “malus” (Latin for “apple tree”), P for “pinus” (Latin for “pine”), A for “abies” (Latin for “fir”), and Qu for “quercus” (Latin for “oak”). An intricate manufacturing procedure mixing sap from Mistletoe obtained in the winter and the summer results in the medicinal extract. The dosage of the extracts depends on the patient’s response as they are given in escalating doses ^[16].

MODE OF ADMINISTRATION:

The most common way to provide Mistletoe extracts is by subcutaneous injection, however oral, intrapleural, intratumoral, and intravenous are other routes of adminsitration. The majority of studies that have been reported used subcutaneous injections two to three times per week, however the overall length of the treatment varied greatly ^[13]. But in some cases, injection site responses, mild reaction, transient pyrexia, and flu-like symptoms. Pseudoallergic hypersensitivity responses during intravenous Mistletoe therapy have only seldom been reported in a dose-dependent manner. Therefore, using Mistletoe presents only minor dangers and appears to be safe, but when used in high dosages, it is important that professionals keep an eye on the patient ^[17].

DOCTRINE OF SIGNATURE:

1. Despite growing on host trees, this plant has a partially parasitic character and is independent of the host in many ways. Similar to a parasite that is independent of its host organ but receives nutrients from it, cancerous cells are comparable
2. The leaves grows in different directions which indicates the undifferentiation of cells in cancer.
3. The node from which the branches arises shows the similarity of solidity of tumor, and also it is more indicated in solid tumors.
4. Once the host tree passes away or when it can no longer provide sufficient nutrition does the Mistletoe die.
5. Potassium is more abundant in Mistletoe likewise it is abundant in malignant tissue ^[18].

VISCUM ALBUM IN VETERINARY HOMOEOPATHY:

Viscum album mother tincture and dilutions are intended for use in all food-producing animals in veterinary homoeopathy. The application adheres to the principles of homoeopathy, in which animals are diagnosed based on an individual pattern of clinical indications. For large animals, the maximum parenteral dose is 10 ml/animal. Although therapy may be repeated, a specific dose plan is uncommon in homoeopathy ^[19].

ARTICLES SUPPORTING THE MISTLETOE AS IMMUNOSTIMULATORY THERAPY IN CANCER:Viscum album, subcutaneously three times a week to 220 individuals with metastatic pancreatic cancer. Anti-cancerous therapy was no longer required for those who had this treatment. No brain metastases was found in the patients. Patients who received Viscum album as an anti-cancerous medication had a 4.8-month increase in survival rate, whereas those who received no treatment had a 2.7-month survival rate ^[20]. 23 studies total—16 randomised, 2 quasi-randomized, and 5 nonrandomized—were found. Out of the 23 studies examined, 12 demonstrated one or more statistically significant positive results (survival or quality of life), another seven demonstrated at least one positive trend (survival, disease-free survival, tumour remission), three revealed no effect, and one demonstrated a negative trend ^[21]. A significant cohort study carried out in Germany discovered that Mistletoe treatment had a beneficial therapeutic impact; the mean survival time was 40% longer in the Mistletoe group (4.23 years) than in the control group (3.05 years; P 0.001) in this study. All of the cancer types under investigation, including small cell or non-small cell bronchogenic cancer, carcinoma of the colon, rectum, or stomach, breast carcinoma with or without axillary or distant metastases, were associated with longer survival times. The study also discovered that Iscador use tends to enhance a patient’s capacity for psychosomatic self-regulation, or the capacity to maintain equilibrium and control under pressure ^[22]. Eight patients were found, seven of whom had bladder cancer that was non-invasive to the muscle and one who with invasive bladder cancer. Before treatment, four patients had tumours that kept coming back. There were 28 occurrences of recurrence among the 8 individuals. The median amount of time without a tumour was 48.5 months. High-dose Viscum album may have had a positive effect in 5 out of 8 patients, was ineffective in 2 patients, and had an unclear impact on 1 patient. The tumour did not progress at all. The majority of patients tolerated the medication well, and none of them discontinued it due to negative effects ^[23].

ROLE OF MISTLETOE THERAPY IN CONTROLLING THE ADVERSE EFFECTS OF CHEMOTHERAPY AND RADIOTHERAPY:

A total of 710 nonmetastatic breast cancer patients got adjuvant subcutaneous Mistletoe extract for three to 52 months out of 1,442 total patients. The authors reported a much lower rate of adverse responses from chemotherapy with Mistletoe therapy after three years of follow-up (16.3% vs. 54.1%). They draw the conclusion that Iscador decreased symptoms related to the disease and its treatment and might increase overall survival ^[24].

Targeted therapy may benefit from the use of formulations that have been shown to reduce the side effects (AEs) of chemotherapy and radiotherapy in cancer patients. It was discovered that individuals getting add-on Viscum album had fewer hospitalisations, grade 3–4 non-haematological adverse effects, and chemotherapy dose reductions in a randomised phase II study involving 72 patients with advanced lung cancer. Using registry data from 310 cancer patients, we recently conducted an observational study and discovered that using Viscum album applications in addition to targeted therapy dramatically decreased the number of AE-related treatment discontinuations in cancer patients ^[4].

CONCLUSION:

This article demonstrates how Mistletoe has an immunomodulatory effect on cancer patients, which increases survival rates, lessens side effects from radiotherapy and chemotherapy, and enhances general health. When medications are administered subcutaneously in high physiological doses, unpleasant consequences can occur, to prevent these side effects, medications can be administered in highly potentized dynamic form. The suggests that the Mistletoe has anti-cancerous properties in both humans and as well as animals.

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