| The word mistletoe relates to not one but hundreds of different
species of perennial, evergreen, parasitic shrubs from different genera.1 “American” mistletoe
is often referred to as Phoradendron leucarpum (Raf.) Rev. & M.C. Johnst.,
or P flavescens Nutt., although there are other species. “European” mistletoe
is Viscum album L., and has three subspecies that are commonly recognised:
platyspermum Kell., abietis Beck, and laxum Fiek.2 V
album has yellowish-green,
leathery, elliptical leaves and inconspicuous yellowish-green flowers.
The fruit is a white, globular, sticky berry, which ripens in December.
Red-berried mistletoe is V cruciatum, which grows on deciduous trees in
southern Europe.
V album grows on many deciduous trees (extracting water and nutrients),
including fruit trees such as apple and lime, throughout Europe, and two
of the subspecies grow on conifers. In England, mistletoe (V album) is
common, particularly in Herefordshire and in the south and south east.
The National Mistletoe Survey, which began in 1994, has been unable to
determine whether or not mistletoe is becoming rarer in the United Kingdom,
although gardens, followed by orchards, are now the most common
habitats.3 Mistletoe is scarce in northern England and is almost unknown
in Scotland, except at Christmas when it may be found in homes and hostelries.
Kiss-mas time
V album was interwoven by ancient peoples into many myths and legends,
several of which survive in some form today. V album and the oak trees
upon which it grew were held in great reverence by the ancient Druids — mistletoe
was believed to protect its possessor from evil, to be an antidote to
poisons and to cure illnesses.4,5 It is
claimed that the Druids used branches of mistletoe to announce the new
year, and that this may explain
today’s use of mistletoe as a Christmas decoration.4
The Christmas custom of kissing under a sprig of mistletoe hung above
a door frame or from the middle of a ceiling is known to almost everyone,
and many of us will have been willing (or not so willing) participants
of this practice at some time. The precise origin of this custom is not
clearly understood. The earliest documented case
in England is said to date from the 16th century, although one suggestion
is that the custom may relate to early beliefs that mistletoe had beneficial
effects on fertility and conception.6 Another interpretation is that an
exchange of kisses is a promise to marry and a prediction of happiness
and long life.5 Allegedly, mistletoe kissing
etiquette requires that a man should pluck a berry from the mistletoe branch
under which he has kissed a woman and that once the last berry has been
plucked, there can be no more kissing. Unwilling potential kissers will
already have spotted how this could be used as a get-out clause, but a
word of warning: hide the berries, do not eat them.
Traditional medicinal uses
Mistletoe (V album L.) is also reputed for its medicinal properties.
For example, it has been used traditionally for lowering blood pressure — although
it is not clear whether this relates to before or after kissing! Some
of the earliest uses documented for mistletoe include treating diseases
of the spleen, complaints associated with menstruation, infertility,
ulcers and swellings or tumours, although it is not clear if V album was the species
concerned.5 Several authors from the Middle Ages, and later, recommended
mistletoe as a treatment for epilepsy and other nervous convulsive disorders.
Part of the rationale for this was that in its growth cycle mistletoe does
not touch the ground, so was deemed an appropriate remedy for “falling
sickness”. Other uses that have been listed include bone fractures
and labour pains.5
More recent traditional uses (for V album twigs) listed in standard pharmaceutical
and herbal reference texts include hypertension, hypertensive headache,
nervous tachycardia, chorea and hysteria.7 The German Commission E monograph
states that mistletoe herb (consisting of fresh or dried younger branches
with flowers and fruits) can be used for treating degenerative inflammation
of the joints by stimulating
cuti-visceral reflexes following local inflammation brought about by intradermal
injections, and as
palliative therapy for malignant tumours through non-specific stimulation.7
Mistletoe today
The use of mistletoe (V album) extracts in the treatment of cancer was
first proposed by Rudolf
Steiner, the founder of anthroposophical medicine, a spiritual and philosophical
approach to health and illness, at the beginning of the 20th century.
Today, mistletoe extracts are widely used in Europe, particularly in
Germany and Switzerland, in the treatment of different types of cancer,
including
breast,
ovarian, urogenital, gastrointestinal, pancreatic and respiratory cancers.
It is used both as an adjunct to conventional cancer chemotherapy and
radiotherapy and,
sometimes, as a single-agent approach.
There have been a number of
randomised clinical trials of mistletoe preparations in the treatment
of cancer, although systematic reviews of such trials have found that
many
of the studies have methodological limitations and have
concluded that there is a lack of evidence to support the efficacy of
mistletoe extracts as a cancer treatment. However, these reviews have
included trials
of several different preparations of mistletoe and the trials involved
patients with different types of cancer. Against this background, a new
systematic review is under way which will categorise included trials
according to tumour type treated and will include sensitivity analyses
according
to the type of mistletoe preparation tested.8
Mistletoe extracts used in cancer treatment usually are administered
by subcutaneous injection and, in some patients, this may cause a rise
in
temperature and skin reactions at the injection site. Preparations for
oral administration are also available. Several licensed mistletoe preparations,
which hold Product Licences of Right (PLRs), are available in the UK
(eg, Iscador products) and mistletoe preparations can be prescribed by
general
practitioners on National Health Service prescriptions. Mistle-aneous preparations
The constituents of mistletoe depend to some extent on the host tree
on which the plant has grown. Moreover, as with other natural products,
the precise phytochemical composition of mistletoe extracts will vary
depending upon geographical, environmental, harvesting and processing
factors. Many different preparations of mistletoe are available and,
for the reasons given, the profile of constituents will differ qualitatively
and quantitatively.
Several manufacturers’ products comprise aqueous extracts of mistletoe
(some
of which undergo fermentation), which
are distinguished according to the host
tree, such as apple, pine or spruce, on which the mistletoe has grown.
Preparations
from different host trees, administered according to different dosage regimens,
are advocated for use in different types of
cancer, although there is no sound evidence base for this. Important groups
of constituents of mistletoe include the mistletoe lectins (high molecular
weight polypeptides) and the viscotoxins (low molecular weight poly-peptides),
both of which have pharma-cological and toxicological effects.9 For
example, there is a vast scientific literature describing the immunomodulatory
and cytotoxic activity of these constituents. Other constituents of mistletoe
include alkaloids and flavonoids.9 Some
mistletoe preparations are standardised on content of certain constituents,
eg, mistletoe lectin-1 (ML-1).
Not berry good
Unlicensed products containing mistletoe are widely available via the
internet. Some of these products contain only mistletoe as an active ingredient
(monopreparations), whereas others combine mistletoe with
other herbs, vitamins, minerals or, as in some traditional Chinese
medicine patent products, animal parts.
Mistletoe berries are poisonous and, in the UK, products made with the
berries must be licensed as medicinal products.10 Although, in practice,
it is highly unlikely that any pharmacist today would be asked to sell
mistletoe berries, at this time of year, visitors to pharmacies might
want to watch out for a sprig or two of mistletoe hanging over the counter!
References
1. Anderson LA, Phillipson JD. Mistletoe — the magic herb. Pharm
J 1982;229:437–9.
2. Foster S, Tyler VE. Tyler’s honest herbal, 4th edition.
New York: The Haworth Herbal Press; 1999.
3. The National Mistletoe Survey. Available at: www.mistletoe.org.uk
4. Leyel CF (editor). A modern herbal. London: Jonathan Cape
Ltd; 1979.
5. Büssing A. Introduction: history of mistletoe uses. In: Büssing
A (ed) Mistletoe: the genus Viscum. The Netherlands: Harwood Academic
Publishers; 2000. pp1–6.
6. Tainter FH. What
does mistletoe have to do with Christmas? APSnet,
December 2002, The American Phytopathological Society.
7. British Herbal Medicine Association. A guide to traditional herbal
medicines. Bournemouth: British Herbal Medicine Association; 2003.
8. Horneber MA, Bueschel G, Huber R, Linde K, Richardson MA, Rostock
M, Kaiser G. Mistletoe therapy in oncology (protocol for a Cochrane
review). In: The Cochrane Library, Issue 4, 2003. Chichester, UK:
John Wiley & Sons Ltd; 2003.
9. Barnes J, Anderson LA, Phillipson JD. Herbal medicines. A guide
for healthcare professionals. 2nd edition. London: Pharmaceutical
Press; 2002.
10. The Medicines (Retail Sale or Supply of Herbal Remedies) Order
1977, Statutory Instrument No 2130.
London: The Stationery Office; 1977.
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