'Niets aan deze plant is normaal', aldus botanicus Karl von Tubeuf die begin 19e eeuw als eerste een uitgebreide monografie schreef over de Viscum album. En het is onmiskenbaar: Viscum album, de Europese mistel, mistletoe of maretak gedraagt zich compleet anders dan andere planten. Er zijn twee dingen die speciaal in het oog springen bij de maretak: de heel aparte 'eigengereide' groeivorm en de extreem langzame groei van de plant.
Namen
Deens: mistelte
Engels: mistletoe
Frans: gui
Pools: jemioła
Portugees: visco
Russisch: омела
Spanisch: muérdago
Zweeds: mistel
Tegendraadse groei: los van de aarde
Wat de eigengereide vorm van de maretak betreft valt direct op dat hij parasitair op bomen groeit en dat hij zich daar manifesteert als een prachtige groene bol, zonder voorkeur voor boven of onder. Zelfs de blaadjes kennen geen verschil tussen onder- en bovenkant. Dat is uniek, want planten groeien in het algemeen in een heel bepaalde richting, namelijk van onder naar boven, tegen de zwaartekracht in, met nieuwe uitlopers naar de zon en met de wortel naar het middelpunt van de aarde. De maretak doet dat anders: die groeit haaks op elke plek waar hij zich op de gastheerboom - vooral appelboom, den, populier - ook maar vasthecht. Hij ontwikkelt zich volgens een eigen ritme, los van de voorwaarden waaraan andere planten zijn gebonden. Het lijkt wel of de maretak is achtergebleven in zijn ontwikkeling als plant naar de aarde toe, waardoor hij niet direct op die aarde kan groeien en de bemiddeling van een gastheer nodig heeft. De maretak is overigens geen echte parasiet, maar een half-parasiet: er is geen sprake van een groei ten koste van de gastheer. Hij onttrekt weliswaar water en zouten aan de gastheer, maar verricht zelfstandig zijn zuurstof - koolzuurassimilatie.
Langzame groei
Heel apart is ook de buitengewoon langzame groei van de maretak: zo verschijnen de eerste blaadjes van de kiemplant pas in het tweede jaar, de eerste vertakking na vier jaar. ledere volgende vertakking ontstaat pas na een jaar. Eerst na vijf tot zeven jaar vormen zich de eerste bloemvormen, die dan na negen maanden (in de herfst) bessen geven. mEr is groei, maar tegelijkertijd wordt die groei binnen de perken gehouden.
Een geneeskrachtige plant met een lange historie
Zoals zoveel geneeskrachtige kruiden heeft ook de Viscum een lange historie. Reeds de Trojaanse held Aeneas verschaft zich met behulp van een maretak toegang tot de onderwereld om zijn overleden vader weer te zien. En in de 'Edda', een IJslands heldenepos uit de vroege middeleeuwen, ziet de jaloerse god Loki kans om met een twijg van de maretak de zonnegod Baldur te doden met hulp van de blinde Hödur. Voor de Druïden is de maretak de meest heilige plant. Uit de eiken-Viscum bereiden zij krachtgevende rituele dranken.
Plinius de Oude in Book XVI schrijft in Engelse vertaling:
"The Druids, that is what they call their magicians, hold nothing more sacred than mistletoe and a tree on which it is growing when it [mistletoe] is discovered it is gathered with great ceremony"
Ook in onze tijd worden aan de Viscum positieve krachten toegeschreven: we gaan geen dieren of mensen ritueel slachten, maar we hangen met Kerstmis boven de deuropening een maretak om ons te verzekeren van gezondheid en welzijn in het komende jaar. Een kus onder de maretak brengt het jonge paar de zegen van gezond nageslacht, zo heet het. In de volksgeneeskunst gold de mistel al heel lang als heilzaam bij menstruatiestoornissen, epilepsie en hoge bloeddruk. De betekenis bij kanker werd pas ontdekt in de 20e eeuw.
Maretak en kanker
De bijzondere vorm en ingehouden groei brachten Rudolf Steiner, grondlegger van de antroposofie, ertoe artsen te attenderen op de maretak als een mogelijk geneesmiddel bij kanker. In het kankerproces lijkt er immers juist een gebrek aan gevormdheid te zijn en manifesteert zich een ongecontroleerde, pathologische groei. Omstreeks 1920 deed Rudolf Steiner voorstellen voor de bereidingswijze en toepassing voor een concreet geneesmiddel. Sindsdien is er continu gewerkt aan de ontwikkeling van een maretakpreparaat. Het was de Nederlandse arts Ita Wegman die als een van de eersten voortbouwde op Steiners aanwijzingen. Samen met anderen ontwikkelde zij het middel Iscar dat later (1926) de naam Iscador® kreeg. Vervolgens verschenen ook andere Viscum-preparaten op de markt. Voor de bereiding van deze middelen wordt gebruik gemaakt van de gehele maretak (inclusief de bessen), meestal afkomstig van appelboom, den of eik. Er wordt tweemaal per jaar geoogst (zomer en winter) en zowel van zomer- als winteroogst worden waterige, gefermenteerde extracten gemaakt. Vervolgens worden deze extracten op een heel speciale manier gemengd, waarbij er nauwkeurig op wordt toegezien dat in het mengsel slechts extracten van één gastheerboom voorkomen, omdat de specifieke eigenschappen van de gastheer een belangrijke rol spelen in de Viscum-therapie.
Naast deze 'antroposofische' Viscum-preparaten kwamen later andere Viscum-producten in de handel. De antroposofische preparaten onderscheiden zich hiervan zowel qua bereiding als qua toepassingswijze (individuele doseringsschema's met series van verschillende sterktes). De niet-antroposofische producten zijn op een bepaalde inhoudsstof gestandaardiseerd, meestal op het zogenaamde mistellectine l (ML-1). De grondstoffen (gehele plant) voor deze preparaten worden slechts eenmaal per jaar, in de herfst of winter, geoogst en stammen meestal van de populieren-Viscum.
Maretak, diabetes, bloeddruk
De gezondheidsbevorderende eigenschappen zouden vooral berusten op de aanwezige viscotoxines en lectines. Er zijn aanwijzingen dat het de insulineproductie kan stimuleren bij type 2-diabetes (ouderdomssuikerziekte). Maar we kennen het vooral als een plant voor een zeer gunstige invloed op hart en bloedvaten en dat het als tonicum kan worden ingezet voor het behoud van een gezonde bloeddruk door zijn inhoudsstoffen: de flavonen, aminen en aminozuren. De meeste recente klinische onderzoeken naar Viscum album zijn voornamelijk gericht op zijn potentieel als anti-kankerbehandeling; echter ten minste drie studies zijn uitgevoerd met betrekking tot hypertensie. In 1990 werd een groep hypertensieve volwassenen behandeld met een kruidencombinatie van Viscum album. De wetenschappers rapporteerden een verlaagde bloeddruk gedurende 3-5 maanden bij de proefpersonen. In een studie uit 2009 werd aangetoond dat een ethanolisch extract van Europese maretak doeltreffend was bij het verminderen van de arteriële bloeddruk. Tenslotte werd een onderzoek gedaan in 2014 waarbij ze zagen dat een behandeling van twaalf weken met een Viscum albumtinctuur resulteerde in een significante daling van de bloeddruk bij proefpersonen. De flavonoïden in viscum omvatten syringin en conferin die op voorzichtig wijze de contractie van de aorta regelen terwijl een andere component, kalopanaxin, hier een ontspannende werking op heeft. Alle flavonoïden hebben samen een tonisch effect op het vasculair systeem.
Bronnen en referenties
Mistletoe: History and Pharmacology, Revised by Chris Smelick
Thompson, Lawrence S.: Norse mythology; the Elder Edda in prose translation, 1974.
Virgil's Aeneid; translated by Robert Fitzgerald; Vintage Books, 1984
Pliny the elder: Natural History; Book XVI
KruidMail Viscum album. Documentenmap door Maurice Godefridi
Als je zelf een maretak wil kweken, is het belangrijk zo vers mogelijke bessen te gebruiken. Laat daarvoor de bessen zolang mogelijk aan de twijgen (en liefst aan de plant op de gastheer....).
Het zaaien kan vanaf eind december tot in maart. Haal pas op het ogenblik van zaaien bessen van de twijgjes. Zaaien van maretak lukt het best op appel, populier, lijsterbes, wilg, meidoorn..... Kies een boom die op een lichte plek staat, want een maretak heeft licht nodig. Wrijf de bessen uit vlak bij de basis van een- of tweejarige tak, die bij voorkeur horizontaal groeit. 'Zaai' bij voorkeur meerdere zaden op een boom: behalve dat je zo je kans op succes verhoogt, heb je hierdoor ook meer kans dat je op termijn toch
in elk geval een mannelijke en een vrouwelijke plant overhoudt. Na een tweetal weken kan het zaad ontkiemen.
Uit de bes komt een kiem, die zich ombuigt naar de tak en daar onder de vorm van een hechtschijfje contact mee maakt. In de loop van het eerste groeiseizoen gebeurt er vervolgens weinig: De rest van het zaad komt los van de tak en komt boven het hechtschijfje te staan, maar verder is er weinig groei te zien. Het plantje heeft bovendien nog geen contact met de sapstroom van de waardplant, en overleeft dus op basis van de reserve in het zaad en van het in de lucht aanwezige water (dit verklaart waarom het zaaien van maretak vooral bij vochtige zomers veel kans op slagen heeft).
In de loop van de zomer groeit er uit hechtschijfje een kiemworteltje dat de bast van de plant doorboort, en dat er voor de winter voorbij is in moet slagen om de sapstroom van de gastheer te bereiken. In april van het volgende voorjaar komen dan de eerste twee blaadjes uit het plantje te voorschijn.
Scientific Name(s): Viscum album L. (European mistletoe) and Phoradendron tomentosum (DC.) Engelm. ex A. Gray (Christmas mistletoe).
Common Name(s): Mistletoe , bird lime , all heal , devil's fuge , golden bough , mistel (German), Iscador
Uses
Mistletoe has been used to treat cancer, although there is a lack of quality clinical trials and no evidence of an effect. Further study is needed. In folk medicine, it has been used for its cardiovascular properties. Clinical efficacy has not been established. Injectable mistletoe extract is widely used in Europe but is not licensed for use in the United States.
Dosing
Crude mistletoe fruit or herb is used to make a tea to treat hypertension at a dosage of 10 g/day. There are a number of proprietary extracts containing low levels of mistletoe lectin-Ι (ML-Ι) used as adjuvant cancer therapies. These extracts usually are given by intravenous (IV) or subcutaneous injection at dosages of 0.1 to 30 mg several times per week. Mistletoe preparations, produced according to anthroposophical methods, are given in incrementally increasing dosages depending on the patient's general condition and response to the injection. Use in pediatric patients has been reported. The pharmacokinetics in healthy adults has been determined.
Contraindications
Data are limited. Use of mistletoe extracts in patients with primary or secondary brain tumors, leukemia, or malignant lymphoma is contraindicated.
Pregnancy/Lactation
Mistletoe contains toxic constituents. Avoid use during pregnancy or lactation.
Interactions
None well documented.
Adverse Reactions
Local reactions following injection include redness, itching, inflammation, and induration at the injection site. Systemic reactions include mild fever or flu-like symptoms. Anaphylaxis has been reported.
Toxicology
Poison centers report toxicity of the whole plant, but especially mistletoe berries. The use of preparations standardized to small doses of ML-Ι or depleted of lectins may reduce toxicity.
The family Viscaceae (Christmas Mistletoe family) contains 5 genera and more than 50 different mistletoe species. Synonyms include Phoradendron flavescens , Phoradendron serotinum , and Viscum coloratum . Mistletoe is a hemiparasitic plant that grows on a wide variety of host trees such as pine, oak, birch, and apple. The term hemiparasitic indicates that the mistletoe plant carries out photosynthesis independently but obtains its water and minerals from the host. There are several subspecies and varieties of mistletoe, which are defined by the host that they parasitize. European mistletoe is dioecious, with male and female flowers on separate plants. They are pollinated by insects and bear small white berries on evergreen foliage. Other varieties bear red berries. 1 , 2
Mistletoe preparations have been used medicinally in Europe for centuries to treat epilepsy, infertility, hypertension, and arthritis. The Celtic priests, known as Druids, revered the oak tree and the mistletoe that grew upon it, according to Roman author and naturalist Gaius Plinius Secundus (also known as Pliny the Elder). At the winter celebration of Samhain, the sacred oaks were bare except for the green boughs of mistletoe. This was taken as a sign of eternal fertility. The Celts placed a sprig of mistletoe above the door of their houses. Its sacred nature prohibited fighting beneath it. This evolved over centuries into the custom of kissing underneath mistletoe at Christmas. 3 In 1921, the Austrian anthroposophical spiritual leader Rudolf Steiner suggested that mistletoe might be used to treat cancer, based on the observation that mistletoe, like cancer, is parasitic and lethal to its host. 4 Swiss and German clinics were founded to implement this idea and are still actively using a mistletoe preparation fermented with a strain of Lactobacillus for 3 days, a process that is more aligned to alchemy and homeopathy than pharmacology. 4 , 5
The most distinctive constituents of V. album are its proteins, which are of 2 types: the viscotoxins, which are small (5 kDa), cystine-rich basic proteins (known as thionins), and the larger mistletoe lectins. Four viscotoxins (A1, A2, A3, and B) have been isolated and sequenced. 6 They are highly homologous 46–amino acid proteins, differing from one another at a few positions. The 3-dimensional structure of viscotoxin A3 has been elucidated by nuclear magnetic resonance methods. 7 The viscotoxin profile of the 3 European subspecies of V. album has been determined. 8 Two novel viscotoxins, termed 1-PS and U-PS, were found in subspecies austriacum (pine) and subspecies abietis (fir). The viscotoxin profile of subspecies album did not vary appreciably with 7 different hosts. The American species P. tomentosum yielded a homolog known as phoratoxin. 2 The preparation Iscador has been shown to contain similar amounts of viscotoxins compared with the unfermented V. album extract. 9
Lectins
Viscumin, a toxic lectin, was isolated from V. album and shown to be a type ΙΙ ribosome-inactivating protein. 10 Three distinct lectins (ML-Ι[viscumin], ML-ΙΙ, and ML-ΙΙΙ) were isolated by another group and shown to have different carbohydrate-binding specificities. 11 , 12 The complete amino acid sequence of ML-Ι B-chain has been obtained, showing homology to other galactose-specific lectins, such as ricin and abrin. 13 The X-ray diffraction 3-dimensional structure of ML-Ι has been obtained in the free state 14 and bound to beta-galactose. 15 ML-Ι binds to several sialylglycoproteins in addition to the galactose-binding specificity initially identified. 16 , 17 The structural features important for carbohydrate recognition have been described in detail. 18 , 19 A minor chitin-binding lectin completely distinct from ML-Ι-ΙΙΙ was isolated. 20 Examination of the commercial preparation Iscador has shown that ML-Ι is modified or degraded, while ML-ΙΙ and ML-ΙΙΙ are still present. 5 , 10 , 21
Carbohydrates
The water-soluble polysaccharides of V. album and Iscador have been purified and characterized. A highly esterified galactouronan and a complex arabinogalactan were identified, with the corresponding polysaccharides from Iscador having lower molecular weights compared with those of the native, unfermented extract. 22
Small molecular weight compounds
The phenylpropanoids syringin, syringenin-apiosylglucoside, and eleutheroside E have been found in V. album , and have been used to identify and standardize mistletoe preparations. 10 , 23 The syringin content of mistletoe growing on different host plants has been measured. 24 A number of known and novel chalcone and flavanone glycosides have been reported from European V. album . 25 , 26 Inositol derivatives are widespread in the Viscaceae family and occur at relatively high concentrations in all species of mistletoe. They are thought to play a role in osmotic balance. 27 Other miscellaneous compounds have been reported. 28 , 29 A report of alkaloids in the plant has not been substantiated by isolation in pure form or structure elucidation. 30
Because of the potential toxicity of mistletoe, many studies have been done in vitro. Methodology of clinical trials is generally poor.
Cancer
Despite a plethora of experiments to determine a mechanism of action for mistletoe, no clear pathway has been identified. Proposed mechanisms generally focus on direct cytotoxic action (apoptosis induction) or immunomodulation (eg, enhanced natural killer cell activity, increased production of interleukins and tumor necrosis factor-alpha, activation of mononuclear cells, stimulation of granulocyte phagocytosis). 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 Therapeutic activity is considered to be caused by mistletoe lectins 65 ; however, other cytotoxic compounds may contribute. 66
Clinical data
Several systematic reviews of clinical trials have been published. 65 , 67 , 68 , 69 , 70 , 71 Outcome measures include survival times, tumor response, quality of life, psychological distress, adverse reactions, and safety. 65 All reviews note the poor methodology in many of the trials; the diversity of extracts (different species, different extraction methods, and different host trees) and the use of various treatment regimens make systematic analysis difficult. No evidence of effect can be shown. A positive and negative trend were found for trials included in the reviews. 65 , 67 , 68 Two quality trials of mistletoe as adjuvant to chemotherapy in breast cancer showed positive effect (quality of life, reduction of adverse reactions of chemotherapy), and 4 trials (including head and neck cancer and melanoma) with good methodology showed evidence of no effect on increased survival. 65 Reviewers considered it desirable to enroll patients in further clinical trials. 65 , 67 , 71 Injectable mistletoe is not approved as a cancer treatment in the United States. 71 Some in vitro and in vivo experiments and clinical studies suggest that interleukins can stimulate proliferation of certain cancer cells, and hence mistletoe therapy may not be without risk in cancer patients. 67 Use of mistletoe extracts in patients with primary or secondary brain tumors, leukemia, or malignant lymphoma is contraindicated. 67
Cardiovascular
In European folk medicine, a primary use of mistletoe is for its cardiovascular properties. However, clinical trials to support this use are lacking. Viscotoxins have been shown to induce reflex bradycardia and possess negative inotropic effects in the isolated animal cardiac muscle, as well as vasoconstriction at higher doses. 72 , 73 Phoratoxin demonstrates action on skeletal muscle fibers. 74 Phenylpropanoids might also play a role in mistletoe's cardiovascular effects through a postulated inhibition of cyclic adenosine monophosphate phosphodiesterase. 75 , 76
Crude mistletoe fruit or herb is used to make a tea for hypertension at a dosage of 10 g/day.
Iscador , a proprietary fermented product with different properties to unfermented mistletoe extracts, contains low levels of ML-Ι (10 mg extract contains 750 ng lectin). 63 Iscador extract usually is given by IV or subcutaneous injection at dosages of 0.1 to 30 mg several times per week. 77 , 78 , 79 , 80 Mistletoe preparations produced according to anthroposophical methods are given in incrementally increasing dosages depending on the patient's general condition and response to the injection. 65 Therapy for solid tumors has used mistletoe preparations containing lectin 20,000 ng/mL or viscotoxins 100 mcg/mL by either the intratumoral, subcutaneous, or IV route. Iscador has not been approved for use in the United States. 81
Use in pediatric patients has been reported. 82 The pharmacokinetics in healthy adults has been determined. 83 Peak plasma concentrations were obtained 1 to 2 hours after subcutaneous injection, and mistletoe preparation was still detectable in some of the volunteers after 2 weeks. 83 An enteric-coated mistletoe-alginate/chitosan complex has been developed to overcome the poor bioavailability of oral mistletoe. 84
Mistletoe contains toxic constituents. Avoid use during pregnancy or lactation. 85 , 86
Clinical trials on adverse reactions related to mistletoe administration ranged from a few reactions to as many as 45% of trial participants experiencing some adverse reaction. 65 , 67 Local reactions following injection include redness, itching, and induration at the injection site. Subcutaneous inflammation following injection of the extract has been reported, 87 and this has been noted as a potential methodological flaw for blinding in future trials. 88 Systemic reactions include mild fever or flu-like symptoms. 65
Mistletoe is considered to be a toxic plant, and its content of toxic lectins lends support to this. 89 Poison centers report toxicity of the whole plant, but especially the berries. Mild gastroenteritis, seizures, hallucinations, and anaphylaxis have been reported. 70 , 90 , 91 , 92 , 93 Use of preparations standardized to small doses of ML-Ι (1 ng/injection) or depleted lectins by fermentation may reduce toxicity. 9
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