Mistletoe in Cancer

Mistletoe
Mistletoe: sacred herb of the Druids. Photo – Stephanie Berghaeuser

Mistletoe leaf (Viscum album) has a long tradition in herbal medicine. It is an evergreen semi-parasitic plant, growing only on trees where it survives by rooting into the branches and sucking sap, vampire-like. It forms large spherical clusters of stems and leaves which can be up to 6ft across, famously on old apple trees but also on hawthorn, ash, oak and many others, though rarely on pear trees. Its name possibly comes from Anglo-Saxon Mistletan; mistle meaning ‘different’ and tan meaning ‘twig’ – as it was clearly not part of the original tree. The Latin viscum means ‘sticky’ – referring to the berries which are dispersed primarily by birds such as the mistle thrush, who, finding the seed stuck to it’s beak, wipes it off onto a branch where the sticky seed lodges. Later the seed will grow a thin root which will penetrate the bark and tap into the living tissue beneath.

Historically mistletoe was a sacred plant of the Druids, who would collect it with great ceremony using a golden knife at a certain phase of the moon. In Norse mythology an arrow of Mistletoe was used to kill Balder, the God of Peace. When the other Gods called for him to be restored to life mistletoe was given the care of the Goddess of Love, and it was ordained that anyone walking under it should receive a kiss – hence the modern custom of kissing ‘neath the Mistletoe at Christmas. [1]. I am left wondering how an arrow, capable of killing anyone, could have been made out of this plant as it has no bark nor really firm structures anywhere, but then probably I, a mere mortal, cannot be expected to understand such niceties.

Mistletoe leaf has a range of uses in the hands of the Medical Herbalist. It is frequently used to lower high blood pressure, where it is safe and effective, partially due to its antispasmodic properties through which arteries can be relaxed. It is gentle enough for long term treatment when this is necessary. It can also be used as a ‘nervine’ in many nerve related conditions and historically was used in epilepsy.

A very significant aspect of the therapeutic uses of mistletoe leaf is its anti-neoplastic properties. Traditionally mistletoe leaf has been used as a strong tea, tincture or fluid extract (an extra strong form of tincture) taken orally for all forms of cancer, but for the past eighty or so years an injectable preparation of this significant herbal medicine has been used, especially in Germany and the German-speaking nations, spreading throughout Europe due to its clear efficacy. The Anthroposophists (Rudolf Steiner inspired medics) have been at the forefront of its promotion and there are now  specialist centres that will carry this out in many countries, including in the UK. One of my young cancer patients is following this path (along with sticking very firmly to a ketogenic diet, and has already outlived, by a wide margin, the prognosis of all her oncologists and doctors) and she recently sent me these published papers on mistletoe leaf in its injectable form known as Iscador. Here they are, with my comments, followed by some other papers using mistletoe leaf in other ways:

1. Mistletoe and Colorectal Cancer [2]

Disease-free survival hazard ratio (DFS-HR) estimated in the mistletoe extract Iscador group (full line) versus the control group (dotted line)

Disease-free survival hazard ratio (DFS-HR) estimated in the mistletoe extract Iscador group (full line) versus the control group
(dotted line)

Friedel et al, 2009, looked at the effects of using injectable mistletoe leaf therapy (Iscador) alongside conventional treatment (chemo- and radio-therapy).They tracked 804 colorectal cancer patients for over 4 years with just over half of these receiving the herbal injections.

The results showed that those receiving Iscador had a lower risk or relapse or death, had fewer and milder disease symptoms and fewer adverse events, compared to the controls,who only received the standard chemo- and radio therapy.

You can see from the graph that the mortality rate in the Iscador (mistletoe) group is lower than in the control group. The graph shows that the Iscador group had a 20% extension in life compared to controls. For a majority of patients that equated to an extra one to four years.

A strength of this study is the size and duration, however a weakness of the study is that it was not randomised.

2. Mistletoe and Breast Cancer [3]

Chemotherapy for breast cancer can leave many patients feeling extremely unwell – severe nausea and vomiting, diarrhoea, headaches, serious fatigue and mental ‘fog’, all of which seriously reduced quality of life. On top of this immunosuppression due to reduction in white blood cells (neutropenia) leaves sufferers prone to infection. Mistletoe, has been shown to significantly reduces the severity of these effects. For example, Tröger et al, report in 2009, a randomised controlled study involving 90 breast cancer patients. They compared chemotherapy alone to chemotherapy and mistletoe treatment over six courses of chemotherapy. The herbal medicine (mistletoe) group showed reduced symptoms and improved quality of life, including better physical, emotional, cognitive and social function, less fatigue, nausea, pain, insomnia and appetite loss. There was a trend towards fewer cases of neutropenia (low white blood cell count), but there were too few participants to reach statistical significance.

A strength of this study is that it was randomised, but weaknesses are that it was rather small scale (90 patients) and was not placebo controlled – so patients knew they were having an additional treatment.

3. Mistletoe and Pancreatic Cancer [4]

12-month overall survival of 220 patients with advanced or metastatic pancreatic cancer assigned to a therapy with extract of VaL (Mistletoe) or to no antineoplastic therapy (Control)

12-month overall survival of 220
patients with advanced or metastatic pancreatic cancer assigned to a
therapy with extract of VaL (Mistletoe) or to no antineoplastic therapy (Control)

Hot off the press is this study, also by Tröger et al, published in 2013. They looked at the overall survival rates of patients with advanced or metastatic pancreatic cancer – one of the most aggressive forms of cancer – when given mistletoe/Iscador alongside conventional treatment. 220 patients were followed for 12 months. You can see in the graph opposite that those on the herbal therapy had a higher survival rate. (BTW , notice how much steeper this graph is compared to the one for colorectal cancers, above, relating to the fact that pancreatic cancer is far more aggressive)The Iscador group had reduced symptoms too with fewer reporting back pain, dyspepsia, headaches, urinary tract infections and abdominal pain. They also developed fewer metastases (i.e. cancer spreading to other tissues).

The medicinal herb, mistletoe – in the injectable form Iscador – was so effective that the ethics committee recommended the trial to be stopped and that all patients be placed on it. Unfortunately, due to licensing restrictions in Serbia (where the trial was conducted) it transpired that it was illegal for patients to be given the mistletoe treatment outside of a trial setting, so instead the ethics committee continued the trial which allowed patients to maintain treatment with Mistletoe!

Strengths of this study were that it was a randomised prospective study, with a large enough cohort to engender confidence in the results.

Can the Ketogenic Diet enhance Mistletoe therapy?

Cancer is being recognised more and more as a metabolic, rather than genetic, or just ‘bad luck’ disease. Due to a metabolic malfunction, in which the mitochondria (energy centres) of the cell become non-functioning, cancerous cells switch to glycolysis – a primitive form of metabolism used by yeasts and bacteria. This makes many cancer cells dependent on glucose as without mitochondria they do not have the ability to switch to other substrates such as fats or ketones for their energy, yet healthy cells can switch easily to these alternative fuels. Consequently a ketogenic diet – high in fat and very low in carbohydrates (which are turned into glucose) – reduces the fuel supply to cancer cells, thus selectively ‘starving’ them, whilst permitting healthy cells to continue to function well on fats and ketones.

So, when working with cancer patients the first thing I do is help them switch to a full-blown ketogenic diet. The ensuing reduction in blood glucose (and therefore insulin) that this instigates brings about a major metabolic shift that goes a long way to undermining the growth of cancerous tumours and malignant processes. In my opinion this is an absolutely essential factor in beginning to reverse cancer. (Interestingly, the same diet is used widely in pediatric medicine to treat children with epilepsy – a surprising overlap with the traditional use of mistletoe leaf for its nerve relaxing properties!)

Tumor weight on (SD-UR) standard diet (SD-UR+2DG) Standard diet + 2-deoxy-D-glucose (KD-R) ketogenic diet, (KD-R +2DG) ketogenic diet + 2-deoxy-D-glucose

Tumor weight on (SD-UR) standard diet (SD-UR+2DG) Standard diet + 2-deoxy-D-glucose (KD-R) ketogenic diet, (KD-R +2DG) ketogenic diet + 2-deoxy-D-glucose

Professor Thomas Seyfried of Boston College, Massachusetts, whose work focuses on the ketogenic diet in cancer, has demonstrated the beneficial action of combining a ketogenic diet with adjunct therapies.

In one study he used 2-deoxy-D-glucose (a non-metabolisable form of glucose) which is known for its anti-tumor effects, to supplement the diet of mice.

The effect on tumor sizes between mice fed a standard diet and those given additionally 2-deoxy-D-glucose (the two bars on the left of the graph above), representing just a few percent reduction. When placed on a ketogenic diet, however, the tumor weight was nearly halved, showing the highly anti-cancer nature of this diet. But the really striking thing about this study was the effect when the ketogenic diet was combined with the 2-deoxy-D-glucose (right hand bar on graph) as there was a huge synergistic effect – reducing cancer growth far more than the therapies when used separately [5]. Similarly, and more recently, the ketogenic diet has been paired with hyperbaric-oxygen therapy to great effect [6]. It seems that ketosis (the metabolic state brought about by the ketogenic diet) places cancer cells under such stress that otherwise ‘mild’ anti-cancer therapies can then deliver the knock-out blow.

The three mistletoe/Iscador trials show beneficial effects in prolonging life and reducing symptoms and side effects. Whilst this represents an undoubted benefit, it is still a long way from a ‘cure’. But how would those trials have looked if the patients had been on a ketogenic diet as well as having mistletoe leaf therapy? I would anticipate we will see the same powerful synergistic effect demonstrated by Professor Seyfried. What we really need now is clinical trials to test these ideas.

There are many other aspects to the research of mistletoe, which are starting to tease out how it exerts its anti-cancer effects. In the studies below oral mistletoe extract was used (more like the tincture that I use as opposed to the injected ‘Iscador’ forms)

Many common chemotheraputic drugs are highly toxic, and perversely, carcinogenic! So it is no wonder that patients often feel that the treatment is worse than the disease. Consequently, researchers are very interested in how mistletoe reduces the damage to healthy cells during chemo. In 2009 two researchers, Sekeroglu and Sekeroglu at a major Turkish university demonstrated that mistletoe extract reduces chromosome damage caused to bone marrow cells by methotrexate, (a common and pretty horrendous chemotherapy drug, and a powerful immune system suppressant) [7]. Another study in 2011 showed that the heart, bladder and chromosome damaging effects of another chemo-drug, cyclophosphamide, were reduced when giving mistletoe alongside it. They concluded that mistletoe reduced oxidative stress and inflammation [8] and found that flavanoids extracted from mistletoe “possess remarkable antinociceptive and anti-inflammatory activities per se without inducing any apparent acute toxicity as well as gastric damage” [9]

Researchers are also investigating how mistletoe slows cancer development. Jean-Paul Duong Van Huyen et al investigated the effects of mistletoe lectins on cancer cells in vitro. [10] They focused on endothelial cells, as cancers usually begin with endothelial dysfunction and angiogenesis (the growth of new blood vessels on which tumours depend) relies on endothelial activity. A hallmark of cancer is that cells become ‘immortal’ – able to divide endlessly, and do not undergo apoptosis, the programmed cell death that protects normal cells when they become irreparably damaged or deranged. They found that mistletoe, caused endothelial cancer cells to undergo increased apoptosis, i.e. proper, healthy behaviour, which they believe may go some way to explain the observed anti-tumour effects of this remarkable herb, mistletoe.

Interestingly, they found that the species the mistletoe grew on (apple, oak etc) affected the degree of tumour suppression. Mistletoe that had grown on oak trees had the greatest effect, returning us neatly to the start of this post, as those wise old Druids held the mistletoe that grew on oak trees in the highest esteem!

My dispensary is never out of stock of Viscum album, as tea or strong tincture, and I am grateful for these researchers, beavering away in their respective universities, for their vindication of the ancient knowledge that medical herbalists like me utilise on a daily basis in their clinics.

References:

  1. Mrs Grieve – A Modern Herbal – 1931/1993
  2. Friedel et al, Clinical Effects of Supportive Mistletoe Treatment in Nonmetastatic Colorectal Carcinoma, Journal of the Society for Integrative Oncology, Fall 2009, Vol 7, No 4 (pdf)
  3. Tröger et al, Quality of Life and Neutropenia in Patients with Early Stage Breast Cancer: A Randomized Pilot Study Comparing Additional Treatment with Mistletoe Extract to Chemotherapy Alone, Breast Cancer: Basic and Clinical Research 2009:3
  4. Tröger et al, Viscum album extract therapy in patients with locally advanced or metastatic pancreatic cancer: A randomised clinical trial on overall survival, European Journal of Cancer, 2013
  5. Drug/diet synergy for managing malignant astrocytoma in mice: 2-deoxy-D-glucose and the restricted ketogenic diet, Nutrition & Metabolism, 2008, 5:33 (full text)
  6. Poff et al, The Ketogenic Diet and Hyperbaric Oxygen Therapy Prolong Survival in Mice with Systemic Metastatic Cancer, PLOSONE, 2013 (full text)
  7. Sekeroglu ZA and Sekeroglu V, Effects of Viscum album L. extract and quercetin on methotrexate-induced cyto-genotoxicity in mouse bone-marrow cellsMutation Research July 4th 2012 (abstract)
  8. Sekeroglu V et al, Viscum album L. extract and quercetin reduce cyclophosphamide-induced cardiotoxicity, urotoxicity and genotoxicity in mice. Asian Pacific Journal of Cancer Prevention, 2011. (full text pdf)
  9. Orhan DD et al, ‘Anti-inflammatory and antiociceptive activity of flavonoids isolated from Viscum album ssp. album. Z Naturforsch Jounal of Biosciences, 2006 (abstract)
  10. Jean-Paul Duong Van Huyen et al Induction of Apoptosis of Endothelial Cells by Viscum album: A Role for Anti-Tumoral Properties of Mistletoe Lectins, Molecular Medicine, 2002 (full text)

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