THE USE OF A MISTLETOE EXTRACT FOR IMMUNOMODULATION AND CANCER THERAPY.Chris Piper BVSc MRCVSSUMMARYThis paper outlines a holistic
treatment for cancer using a whole mistletoe extract (Viscum album L), in
combination with other complementary
therapies. From the holistic perspective,
cancer is considered a disease of the whole organism. The integrity of the
organism and its homoeostatic mechanism has been overwhelmed by a combination
of external insults, deficiency states, disturbances of metabolism, and organ
malfunction. The immune system is particularly affected and fails to
distinguish between self and non-self
and cannot differentiate
between alien or defective cells and normal cells. The cancerous process is
the chaotic and final stage in a progressive sequence of faulty cell
development, with neoplasms resulting from reversion to an undifferentiated
state, and with progressive liberation from the control mechanisms. Whole extract of mistletoe
counteracts the immunological deficit associated with cancer by enhancing
immune function through cytokine-mediated immuno-modulation. Clinical
responses to therapy include enhanced well being of patients, slowing down or
cessation of tumour growth, regression of tumours, and prolonged survival
times. Helixor® mistletoe preparations are
approved for adjunctive treatment of cancer in humans in Germany and in
several other countries. The author presents data collected from his
experience treating cats and dogs with Helixor® during the last nineteen
years. INTRODUCTIONBiologic therapies, such as
mistletoe therapy, are growing in importance for the treatment of humans with
cancer, and are used as an adjunct to standard modalities of surgery,
radiology and chemotherapy. Paradoxically, conventional therapies are
tumour-centred and immunosuppressive, whereas biologic therapies are
organism-centred and immunostimulative. However rational and necessary
conventional oncological approaches may be, they undeniably impose an
additional burden on the already compromised immune system of the cancer
patient, thereby exacerbating the existing immunologic deficit. Their benefit
is particularly doubtful for patients with metastases or inoperable primary
tumours. This paradox imposes a dilemma for the therapist. Conventional
therapies such as chemotherapy and radiotherapy may negate the benefits of
biologic therapies, however; studies show that biologic therapies can reduce
the side effects of these conventional therapies and enhance wellbeing and
extend survival time of human patients (1). Biologic therapies are a rational
option in addition to primary oncological therapy to help prevent relapse, metastasis
and to support palliative care. The goal of treatment is immuno-modulation,
regeneration of healthy tissue, improvement of the quality of life, better
tolerance of aggressive conventional therapies, and prolongation of life. The concept of holistic cancer
treatment in humans embraces diet, lifestyle, psychological counselling and
biologic therapies. Treatment with whole mistletoe extracts over the last
thirty years has developed a reputation as a mainstay in the adjunctive
biologic treatment of cancer. Whatever the perspective and approach to cancer
treatment is, it is important to be mindful of the insidious nature of cancer
and its overt clinical appearance usually months or years after initiation. CURRENT KNOWLEDGE OF MISTLETOE THERAPY IN HUMAN
MEDICINE In 1921 Dr Rudolf Steiner, the
founder of anthroposophy and anthroposophic medicine, was the first to give
his indications for the use of preparations from the European white-berried
mistletoe (Viscum album L) in the treatment of cancer. The efficacy of
mistletoe therapy in human medicine is documented in numerous scientific
publications and supported by decades of clinical use. A monograph on Viscum
album produced by the former Commission C of the German Federal Health
Authority (2) summarised its effects as follows: ·
Improvement
of the general condition and wellbeing in most patients independent of the effects of the cancer ·
inhibition
of cancer growth without adverse effects on normal tissues ·
Prolongation
of survival time. ·
Elevation
of body temperature ·
Relief
of tension and depression ·
Mitigation
of tumour associated pain HISTORY OF MISTLETOE (Viscum album,
family Loranthacae) The European white-berried mistletoe
is one of many plants whose extracts have been used in medicine. Historically, mistletoe-bearing oaks were
holy to the early Germanic tribes.
Their priests, the Druids, wearing white robes, would harvest the
mistletoe with a golden sickle, catching it in a white cloth to prevent it
touching the earth. Mistletoe was
considered a remedy for all diseases and throughout the Middle Ages was used
to treat epilepsy, sterility, high blood pressure and depression. The extraordinary nature and
behaviour of this plant are worthy of mention. The growth of mistletoe defies
the expected pattern of plant growth, which, in some ways, is reflected in
the unregulated growth of cancer. It
is semi-parasitic, taking only water, mineral salts and traces of organic
substances from its host. Mistletoe
cannot grow on the earth nor can it flourish on every tree. It retains characteristics of both plant
and animal, containing the amino acid arginine, which is rarely found in
plants, and lacking glutamine and asparagine, which are found in all other
plants. Unlike most plants, it shows
no heliotropism or geotropism; that is, it does not grow towards the light
nor is there a tendency for the roots to grow towards the centre of the
earth. Furthermore, it follows its own seasonal rhythm out of line with other
plants, flowering in winter and fruiting in summer. Other features express its primitive
nature. The plant grows by dichotomous branching, does not form bark, the
leaves have no upper or lower surface, and do not wither and fall during the
first four years. Chlorophyll is
present throughout the plant, even in the areas not exposed to light. Unlike other plants it germinates in the
light and, without displaying a latent period before germination, may begin
germinating while still in the berry. It has been described as a survivor of
an earlier period (Old Moon Period) in the evolution of the earth when
plants, at a stage between our present plants and animals, could live. Rudolf Steiner, founder of spiritual
science in the 1920s, recognised the unusual qualities of this plant. He
called it “insane aristocracy”. He
described three formative forces; etheric, astral and ego, which shape the
cellular structure of the physical body.
These forces compel the specialisation of cells to constitute the
organs of the body, and regulate their functions. A weakening or disruption of these forces
allows cells to escape control and develop “autonomous cellular propagation”
(3). In 1917 Steiner gave an
indication for the use of mistletoe in cancer treatment. “The emancipation of
the mistletoe from the spatial and chronological order governing its
environment can be seen as reflecting the characteristics of tumour cells
which rebel against the order governing the function of the organism by
liberating themselves from its regulatory processes”. Helixor® is a non-fermented, whole
liquid extract produced from blending four seasonal harvests of
mistletoe. It is unprocessed, and
undergoes micro-filtration to achieve sterility. The four seasonal extracts are blended in
an egg-shaped vessel where a vortex has been created by an impeller. The special whirling process enhances the
potency of the extract and is reminiscent of the stirring method used in the
preparation of the biodynamic preparations 500 and 501 used in biodynamic
farming. There are three kinds of Helixor® corresponding to the three
different botanic subspecies of Viscum Album L: Helixor® M from the apple tree, Helixor® A from the fir tree, Helixor® P from the pine tree. The three preparations show some differences
in their therapeutic effects as well as their biochemical profiles. Helixor®
M induces the greatest reaction (fever and local swelling) and causes the
greatest tumour inhibition and inflammatory stimulant effects. Helixor® A shows
the least reaction and is the best
tolerated and has the most potent immunoprotective and roborant effect. Helixor® P comes somewhere in between these
two, and is the one preferred by the author. Helixor® is provided in glass
ampoules of varying concentrations from HELIXOR Heilmittel GmbH & Co. KG,
Germany. There are several other commercial preparations of mistletoe
available. BIOLOGIC THERAPYBiologic therapy is now regarded by
oncologists as the fourth modality after surgery, radiation and
chemotherapy. It refers to those
cancer treatments that produce anti-tumour effects by stimulating host
defences. Activation of the host’s
reponses occurs through modulation, augmentation and restoration of immune
function as well as direct anti-tumour activity. There is also a protective
effect on normal cells against the adverse effects of other cancer therapies. Biologic therapies trigger the
immune cascade. This immune cascade is
instigated through phagocytes, natural killer cells, and T and B lymphocytes. In addition to these cells, a number of
lymphokines play an important part in immune activity. Cytokines such as tumour necrosis factor
(TNF α), colony-stimulating factors (G-CSF and GM-CSF), and
interleukin-2 (IL2) have all been studied in veterinary oncology (4). Helixor® has been shown to have an
immuno-modulating, anti-mutagenic and immuno-protective action. Specifically it increases the number and
activity of natural killer cells and neutrophils; it induces cytokine release
(TNFα, IL1, 2 and 6) (5,6,7); it increases γ interferon (8); it is
cytotoxic (in vitro); it has a DNA stabilising effect; it stimulates T cells
and the production of GM-CSF (9); it enhances new collagen formation and
inhibits collagenase activity of cancer cells; it increases fibroblastic activity
which restores matrix (10); and it
protects peripheral blood lymphocytes against chemotherapy-induced mutagenicity
and immunosuppression (11).These effects explain many of Helixor’s clinically
established effects of fever, leucocytosis, release of CRP and other acute
phase proteins, and stimulation of medullary haematopoeisis. These tumour growth inhibiting effects
result in a slowing down or cessation of tumour growth. A number of biologically active substances
in Viscum album have been described (12,13). The predominant constituents are
carbohydrates (oligosaccharides and polysaccharides), proteins (lectins),
amino acids (especially arginine), and flavenoids. Some constituents have
specific effects; however, the whole extract has been shown to be the most
effective formulation for cancer therapy. A combination of mistletoe therapy
with radiotherapy or chemotherapy is beneficial. It has been shown that the
side effects of nausea, vomiting, bone marrow suppression, and
immunosuppression can be reduced by concurrent mistletoe therapy. Moreover,
there is less need to interrupt antineoplastic therapy because of bone marrow
depression. Studies also show an improvement of quality of life and survival
times for human patients treated with a combination of chemotherapy and
helixor compared to chemotherapy alone (1). An increasing number of clinical trials on
mistletoe therapy are available to support the efficacy of this cancer
treatment. Kienes`s critical analysis showed that four out of six studies
confirmed statistically significant results when groups of patients were
compared with their respective control groups (14). INDICATIONS FOR HELIXOR (in humans)Helixor® is indicated in humans for
the following situations : ·
As
an adjunctive and palliative therapy for inoperable solid tumours (carcinoma,
sarcoma, melanoma) and systemic malignancies (lymphoma, leukaemia). ·
As
a preoperative or postoperative therapy to help prevent relapse and
metastases. ·
Precancerous
conditions (cervical intraepithelial myoplasias,chronic hepatitis B and C,
ulcerative colitis, intestinal polyps) ·
Treatment
induced myelosuppression (aplastic anaemia) Contraindications for use are
allergic reactions to Helixor® are persistent high fever, severe inflammatory
disease, pregnancy, and severe hyperthyroidism. Pronounced allergic reactions
are very rare. MISTLETOE THERAPY IN CATS AND DOGS The author has used Helixor®
extracts since 1984 for treating cancer in cats and dogs. He has modified the
human protocols to suit veterinary medicine and provide ease of use for
clients who are responsible for implementing the treatment. Clients give the
injections and record daily temperatures at home. CASE SELECTIONEffective treatment requires a
dedicated commitment from veterinarian and client. Careful observation, high
motivation, compliance, and willing co-operation from the client are
essential to the effectiveness of therapy.
Patients should be selected carefully using the following criteria:
A realistic appraisal should be given at the outset along with any ethical requirement to inform the client of the unorthodox nature of the treatment. The veterinarian should provide caring support, an honest assessment of treatment, and be accessible to the client at all times especially during the first three weeks of treatment. Because it is difficult to predict the progression of this disease and the individual’s response to treatment, it is important to maintain close communication with the client and provide frequent assessment of the patient to ensure that the quality of life of the patient is protected. TREATMENT PROTOCOLTreatment commences with daily
subcutaneous injections starting with 1.25mg and increasing in 1.25-2.5mg
increments until a reaction occurs. The author uses either 50 unit (0.5cc) or
100 unit (1cc) insulin syringes to aspirate the contents of a 100mg ampoule
(2cc) of Helixor® P. Alternatively, the contents of an ampoule can be
transferred to a 3cc vaccutainer without additive (yellow top) or an empty
vaccine diluent vial, which must then be stored in the fridge. The daily dose
can be aspirated from the vial. The appearance of flocculent material is
indicative of fungal contamination and the contents should be discarded. Injections are given subcutaneously
on both sides of the body between the neck and costal arch. Injection sites
are rotated to avoid giving injections in the same place twice. These sites
are chosen for ease of administration; however, it is often preferable to
inject as close as possible to the tumour and may, in some cases, be more
beneficial to inject into the tumour. Marking the site of injection by
marking the fur with a felt-tipped pen helps identify where injections have
been given. The reaction manifests as a fever
and/or a localised swelling at the site of injection, and the animal may also
show malaise and inappetence. At the
onset of these symptoms, assuming that they are related to the therapy and
are not paraneoplastic in origin, the dose is kept the same as the previous
one until these signs abate. If the
fever is marked (>39.5°C) or lethargy persists, no further injections are
given until the fever abates and demeanour improves. By constantly measuring
rectal temperature in the morning and evening and recording it graphically, a
pattern of response can be observed.
The fever response can be detected several hours after injection and
usually peaks around eight hours after the injection, but may persist for
more than twelve hours. If the temperature in the evening is
elevated (>39°C), the dose the following morning remains the same as the
previous morning. If the temperature in the evening is normal, then the dose
the next morning is increased. If the temperature on the following morning,
twenty four hours after the injection, remains elevated (>39°C), then no
injection should be given that day. The peak fever can vary by several hours
for individual animals. This fever
response normally occurs at a dose of 2.5mg-5mg and may persist for two weeks
until the dose has reached 10-15mg. The degree and duration of the fever, in
association with the clinical demeanour of the patient, are the main
parameters used to determine the progression of treatment. A persistent fever
may reflect another cause, either a paraneoplastic condition, tumour necrosis
or some other concurrent disease. During the reactive phase some loss of body
weight may occur. Appetite and demeanour may be significantly enhanced
following this phase. Once the
reaction to injections has ceased, the dose is then increased by 5mg
increments until a dose of 50mg has been achieved. The reactive phase seldom
lasts longer than 2-3 weeks and it is during this time (a window of
opportunity) that the immune cascade is best stimulated. Concurrent drug treatment may affect
the development of a fever response. Non steroidal anti-inflammatory drugs
are effective anti-pyretics and corticosteroids may also interfere with the
therapeutic benefit. It is advisable to stop this medication if possible, at
least for the first 2-3 weeks during the reactive phase. Once a dose of 50mg has been
achieved a rhythmic dose sequence is instituted. The frequency of injections is reduced to
every two or three days, and the dose is rotated from 50mg to 75mg to 100mg
and repeated. Following several cycles, and depending on the response to therapy
and the malignancy of the tumour/s, the frequency of injections is reduced to
weekly, then to monthly, with the dose being maintained between 50mg and
100mg.
ADJUNCTIVE SUPPORT It is helpful to provide additional
support for the body, especially during the reactive phase, as this protects
against free radical damage and encourages immune modulation. This is
particularly important when concurrent chemotherapy is used. The author uses
a comprehensive antioxidant formula, high levels of vitamin C, and a mushroom
extract. Dietary advice includes the use of a high protein, high fat and low carbohydrate foods preferably prepared at home from fresh raw meat and cooked or raw coloured vegetables (carrot, beetroot, broccoli, beans, pumpkin). Cold pressed oil can be used to increase the fat content of food (flax oil 5cc/10kg). Other modalities such as homoeopathy, acupuncture, herbal remedies and nutraceuticals can also be used. MONITORING
TREATMENT In addition to measuring daily
rectal temperature, local skin reaction and general demeanour, the monitoring
of haematological indices is valuable. A complete blood count will often show
a moderate leucocytosis with a left shift. The rate at which the dose can be
increased and the frequency at which injections can be given is determined
by; • The degree of fever and local
reaction • The tumour size; the rate of
tumour growth and tumour malignancy • The animal’s health; any
debilitating, paraneoplastic or concurrent disease. A local swelling greater than 4cm in
diameter or a fever over 39.5°C is excessive. Where there are prolonged and
debilitating reactions and/or large local swellings over the injection sites,
the following options can be considered: • Reduce the incremental dose from
2.5mg to 1.25mg • Miss a day or give injections
every second or third day • Change from Helixor® P to Helixor®
A. Once the reactive phase is over Helixor® P can then be substituted. These side effects of Helixor®
treatment constitute an excessive manifestation of the desired inflammatory
and immunostimulatory effect, and can be controlled by adjusting the dose and
frequency of injections. Local subcutaneous swelling is indicative of delayed
cellular responses and shows that the immune system is responding. A fever is
an indirect indication of the release of interleukin-1 from macrophages,
marking the start of the immune cascade. Occasionally there may be regional
lymph node enlargement. Clients may regard these local reactions as
debilitating for their animal; however, if they are made aware of what to
expect, that the response to treatment is evidence of efficacy, and that the
reaction is transient and should not last longer than 2-3 weeks, then most
are willing to persevere. The response to Helixor® therapy is
primarily dependent on the patient’s capacity for mustering an immune
response. While there may be some direct effect on the tumour it is the
stimulation of immunological, regulatory and regenerative processes that
constitutes the main benefit of therapy. Significant individual differences
in response and course of disease necessitate individualised treatment
regimens. Where an allergic reaction occurs,
seen as generalised urticaria or persistent swelling at the injection site
for more than two weeks, then desensitisation should be instituted.
Desensitisation using Helixor® A in minute doses of 0.1mg should be given
twice weekly until there is no appreciable skin swelling. To date the author
has not seen any allergic reactions. Surveillance using radiography,
sonography and digital palpation are useful for monitoring response to
treatment. Where appropriate, callipers can be used to directly measure the
size of superficial tumours. The duration of treatment is
variable and depends on: •
Other concurrent therapy being used • The presence of
secondaries •
The prior use of surgery and whether it was successful • The malignancy of
the tumour • The degree of tumour
reduction seen since treatment commenced Where surgery has succeeded in
complete removal of the tumour or tumours and there has been no recurrence,
treatment may stop after twelve months. Where there has been incomplete
surgical excision, tumour recurrence or continued growth, high malignancy or
the presence of secondaries, then Helixor® treatment should be maintained
indefinitely. As well as the effect Helixor® has
on the tumour it is important to recognise the benefits of enhanced well
being. Patients often show improved appetite and demeanour and take up
activities that they have not displayed for some time, such as chasing the
ball or barking at visitors. Amelioration of the symptoms of concurrent
diseases such as arthritis and dermatitis may also occur. CASE REPORT - LIVER CARCINOMA IN A CATOn the 16th October 1985 a 3cm diameter palpable liver tumour was diagnosed in Candy, a 13 year old cat. Candy’s liver enzymes were elevated and weight loss and polydypsia were evident. Treatment with Helixor® A began on the 16th October 1985 commencing with a dose of 2.5mg and increased daily by increments of 2.5mg. When a dose of 50mg was reached the frequency of injections was reduced to every second or third day. Concurrent supportive treatment with the antioxidant selenium ACE and the homoeopathic remedy lycopodium was given. The owner administered a fresh extract of aloe vera regularly. After 2 weeks the cat’s appetite was good and no increase in tumour size was palpable. On the 13th November 1985, one month after commencing treatment, no hepatic mass could be palpated. The dose at this stage was 12.5mg. The tumour was again palpable on the 16th December 1985 but despite this Candy was in good health. On the 30th December 1985, the cat was operated on for the removal of a gastric furball. Observation of the tumour at surgery determined that it was inoperable and the prognosis was poor. The tumour continued to grow over the following four months reaching 4cm in diameter. A year later in December 1986
Candy was again operated on to remove a gastric furball. A cystic 6cm mass
was removed from the liver at the same time and was confirmed histologically
as a hepatocellular carcinoma. Histologically there was extensive necrosis,
vacuolation and degeneration with a mild to moderate host immune
response. Multiple liver secondaries
were also observed at this time.
Extensive invasion of the portal fissure was observed and an extremely
poor prognosis given. Helixor® was maintained at 50mg fortnightly
and Candy`s condition remained surprisingly stable. No tumour was palpated in October 1988 but
by February 1990 the tumour had regrown. The tumour continued to grow slowly
over the following eight months during which time Candy received 50mg
Helixor® every month. The frequency was increased to weekly but by the end of
January 1991 the tumour had increased further in size. Candy died peacefully
at home on the 10th February 1991 at the age of 18½ years of age, five and a
half years after the diagnosis and commencement of Helixor® therapy.
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