Mistletoe, it’s not just for kisses! Is it poisonous? At a low dose, can mistletoe be used as a medicine?

PODCAST TRANSCRIPT: Medical Mistletoe

Hello. I’m Anne Renwick, steam punk romance author. Welcome into the laboratory. This is episode number five, Medical Mistletoe. Today I’m going to talk about where the very first ideas for A SNOWFLAKE AT MIDNIGHT originated.

When I decided to write a Christmas story – which was at first supposed to be a short story, which soon became a novella, and then ended up as a short novel – I started looking around to see what kind of medicinal properties I could find among the various spices used in holiday cooking, and there were quite a few. For example, ginger makes a brief appearance in the story in A SNOWFLAKE AT MIDNIGHT, as it’s reported to have a number of therapeutic qualities, among which are anti-inflammatory properties, anti-nausea effects. It goes on and on, but the research data wasn’t strong enough for me to work with. But if you’re curious now about the properties of ginger, I’ll link to the paper I found and then you can delve into its properties in more depth on your own.

So if not spices, what else could I work with? I started looking at the plants that are associated with Christmas, such as deck the halls with balls of holly, and I looked at ivy, and of course I looked at mistletoe because who doesn’t think about mistletoe kissing under the mistletoe? So very classic, a Christmas scene. But mistletoe hasn’t always just been about stealing a kiss beneath it. Mistletoe has a longstanding presence in folk medicine. In fact, it has about 1000 years, maybe more years of tradition. And it had its origins in protecting against evil spirits and promoting fertility, hence the kissing.

So what is mistletoe exactly? Well for those of us here in the United States, we’re going to have to sit up and pay a little more attention. For example, when I lived in Savannah, Georgia many years ago, one of the things you could see in the trees in the winter when there were less leaves, there were these funny ball-like plants way, way up in the tops of the trees. I quickly figured out that they were mistletoe. And, of course, all we know is mistletoe as a general term. Right? So cool. That’s the kissing kind, right? I assumed that. I was probably wrong.

The mistletoe native to North America is not at all the same kind of mistletoe that is native to Europe. No. What we have here in the United States is a plant that’s from an entirely different family. We call it mistletoe. Generally speaking, the term mistletoe is being applied to plants that look similar and share similar growing habits. I equivocated a little there about us not having the same kind of mistletoe in Europe because European mistletoe, which is native to Britain and much of Europe, was actually introduced to Northern California in the year 1900. So has the European species, made it all the way across the continent to reach Georgia? I have no idea. If you’re a botanist or you have knowledge of this, I’d love to know. Let me know.

So the European mistletoe, the original mistletoe where all the plants got their name from, goes by the genus species name Viscum album. And that’s the kind of mistletoe we’re going to talk about today. It’s the one with all the medicinal properties that we want to discuss. So let’s start by talking about Viscum album, the European mistletoe and its properties.

What are its characteristics? It has smooth edge leaves that are both oval and evergreen. These leaves, you’ll find them in pairs along the stem, and the kind of berries it produces are waxy and white, and they appear in clusters of anywhere between two and six pairs at a time that will ripen in the winter. Mistletoe grows in a number of different kinds of trees. Oak trees, Apple, Maple, Birch, Ash, Lime, and that’s just to name a few. Mistletoe is semi parasitic, which means it’s using a root-like structure that’s called a haustorium to tap into the tree’s vascular system, the pipes, if you will. Because of this, mistletoe can be really harmful to a tree, especially if the tree is really young, or small, or if the tree becomes really overwhelmed by a lot of plants. If you see a tree completely covered and mistletoe you have a problem.

So for our first diversion, remember those waxy white berries I just mentioned? They’re very sticky and, in fact, mistletoe and sometimes the boiled bits of holly bark were and still are, (but rarely) used to make something called birdlime. This is a substance, defined as a sticky substance spread onto twigs to trap small birds. Yes. You’re guessing, right? Those trapped birds are destined for the cooking pot. That’s a nasty little trick that’s now illegal in most countries. But another diversion about birdlime in World War II. Birdlime was actually used to make a something called a ‘sticky bomb’. It’s a kind of hand grenade that would stick to tanks. They were desperate to stop the progress of these tanks, so someone came up with an idea from their childhood. What about bird lime? Well, that was great. But there were some problems. It didn’t always stick. If the tanks were dusty or dirty. And worse, the bird lime sometimes made this bomb stick to the user, so they set that aside. Also, has anyone else read The Twits by Ronald Dhal?  It made me think of that book, because there’s that horrible character in there who spreads the glue on the branches of a tree to trap birds. And these birds end up in a pie in the story. No? Well, I’ll link to it in the notes. If you’re curious.

Let’s move onward.

Back to mistletoe, to the original European variety Viscum album. Historically, it’s used as a cure, can be traced back all the way to the time of the Druids. Now, as the Druids had an oral tradition for passing on their knowledge, we don’t have any information that came from them directly, but there’s a Roman author called Pliny the Elder, who recorded a lot about what the Druids were up to, or at least what he thought they were up to. And among the Druids, the Oak tree was the most sacred tree. So therefore, mistletoe that grew in the Oak tree was obviously the best kind of mistletoe. So the Druids considered mistletoe, a kind of cure all, and they had a very specific way of going about collecting the mistletoe. The ceremony is written down from the viewpoint of Pliny the Elder. He records that white robed Druids used a golden sickle to cut the mistletoe from the tree, which was then caught in a white cloth. Caught in a white cloth? This is because the Druids apparently believed that if the mistletoe touched the ground, it would lose all its properties.

Mistletoe as a cure all? Well, that’d be nice. If it were true, we’d all be using mistletoe all the time. We’re not. Let’s get into some of the details about what mistletoe can and cannot do.

We’ll start with what the Druids thought it could do. They believed it was an antidote to all poisons. No, not so much. They also believed it could be used to promote fertility in barren animals, not just humans. And, in fact, there is some evidence that it can be used to stop uterine bleeding, such as a painful menstruation or when a spontaneous abortion is threatening. And there’s another cure that’s not linked back to the Druids themselves, but mistletoe was thought to be able to cure epilepsy. Does it have neurological effects? Yes, it does, but those effects are poorly defined even today, and it is most certainly not an epilepsy cure.

So. I really liked the idea of using mistletoe in my story and decided to dive down this particular rabbit hole, to chase the possibilities that it could be used to promote fertility, to cure epilepsy. And that’s when I found out that that really wasn’t going to lead me anywhere. That the research evidence for such effects was really kind of sketchy. And even then, the plots I was coming up with weren’t really leaping to mind.

But then I started to find some research articles suggesting that mistletoe might have an effect when it’s applied to disorders of the immune system. Now poison is in the dose. You’ve probably heard that from me somewhere before. A little bit of poison can be sometimes be medicine.

So is mistletoe poisonous?

Most certainly it is. If you consume enough of it, so don’t, okay? Don’t go consuming mistletoe thinking it’s a cure all like the Druids thought. But mistletoe does have certain kinds of cytotoxic effects. Cytotoxic “cyto” means “cell”.  “Toxic” is “toxin”. So yes, it can actually poison cells. So stick with me as I give you some science-y, biological phrasing here. Ready? Mistletoe has lectins that bind to very specific carbohydrates and inhibit translation at the ribosomal level. That’s for you, science people who are in biology. Basically, it stops your body from making proteins. That’s toxic. That will kill you if you hit yourselves with enough mistletoe all at once.

If we use the right level of mistletoe extract with these lectins, can serve as a kind of cure, as a kind of treatment for something? Well, here’s what the research shows us. Mistletoe lectins can increase the number and cytotoxic activity of natural killer cells. Basically, this means it can help boost the immune system response. Mistletoe can increase the number of other cell types that stimulate the immune response. Injections of mistletoe extract can cause something called mild eosinophilia. In other words, it can cause an increase in cell types that are involved in allergic reactions and inflammation. With regards to cancer, it’s been found that mistletoe extract can increase nonspecific antitumor activity, meaning it can’t target a specific kind of cancer. Nonspecific antitumor activity.

If we think about it, the use of mistletoe in ancient times to treat some sort of cancer, was to treat a tumor. In those times they were not treating tumors that were internal, but they were treating tumors that were more on the surface, much like in my story. And, therefore, the treatments that they would have developed would be of a topical nature.

Are we using mistletoe in modern medicine? Not so much, but there are commercial extracts available in Europe that are used as something called an adjuvent therapy. That means in addition to not instead of standard cancer treatments. So please. Please, please, please, do not think that the recipe in my book is an actual way to treat skin cancer. See your doctor if this is an issue.

But what if you want to try this mistletoe extract therapy as an adjuvant in addition to a normal cancer treatment? Well, if you live in the United States or Canada, you’re pretty much out of luck. It’s very rare that they’re using mistletoe extract here. So unless you live in Europe, oh well.

Okay. So with regards to my story,  at this point while I’m digging around, looking at everything I can find about mistletoe and how it may or may not be used in medicine, I stumble upon a medical paper that documents the actual use of mistletoe extract and only mistletoe extract to cure a case of cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma is a cancer that when it develops, is common in sun exposed areas. Sun exposed. It’s a locally invasive cancer that rarely metastasizes, which means it’s not likely to leave wherever it develops and travel around. Say it’s on your face. It’s not going to pick up, hit the bloodstream, and take off to land and say your liver or any other organ or location.

Cutaneous squamous cell carcinoma has a low fatality rate of about 1-2% though, once you develop it, there is a 50% chance of more lesions developing somewhere else over time. So what do you do about cutaneous squamous cell carcinoma? The first line of treatment is surgical excision. You remove it. That’s basically the beginning and the end of the treatment.

So how does this tie into mistletoe extract? Well, this paper was reporting a single case (n=1) of an older gentleman who was 78 years old and had refused surgery for health concerns. Someone apparently managed to talk him into trialing a Viscum album extract to treat his skin cancer, and he agreed. So what they did, to summarize this huge paper, is 10 months of injections at the lesion site – and he went into spontaneous remission. At the time this paper was written, he’d gone for four years with no recurrence of this cancer.

I thought, wow, cool. I can work with this paper. This has plot written all over it. And if you’ve read A SNOWFLAKE AT MIDNIGHT, you’re probably going, “Oh, I see now.”

Okay. So I have linked to the paper in the show notes, If you want to take a closer look. This paper, while I was reading through it, also mentioned that this Viscum album extract came from a mistletoe plant that had been grown on an Ash tree.

Hmm.

Remember? I talked about how mistletoe plants grow on trees? They use those root-like structures called haustorium to sort of dig into the bark, dig into the vascular tubing of the tree so they can extract nutrients from the sap that’s flowing through the branches?

If you think about it, it makes sense that they would list the kind of tree that that particular mistletoe plant had been growing on, providing the mistletoe plant with nutrients. Different species of trees are going to provide different nutrient profiles, sort of like one vitamin pill versus another may have some more of this nutrient, less of another, or may include an entirely different ingredient that the other vitamin pill doesn’t include at all. So these trees providing nutrients, different species, different chemical makeups, it will have a different nutrient profile. And this also depends, perhaps, even on the soil they’re growing in which they’re growing, what time of the year the mistletoe plant happens to be harvested. And, oh yes, the companies I mentioned who are making that adjuvant therapy of mistletoe extract, yes, they were well aware that the kind of tree, the mistletoe grew on impacted their product.

The companies very specifically list how their extract is made. They very specifically list which host tree their mistletoe was grown upon, and they list what time of the year that mistletoe plant was harvested. For example, Iscarorm, a patented mistletoe extract, is made from Apple trees. You can look them up. They’ve got very specific details on exactly how their product is made.

I thought, Hmm. Okay. Apple trees. Circling back to where I was going with plenty of the elder and the Druids thinking the Oak tree was really, really special. I really wanted my mistletoe be grown on an Oak tree. I really wanted this. So I went digging around and I found this really, really interesting paper where they collected them (mistletoe) from six different trees and did a chromatography profile, studied what kinds of phenolic acids were in each product. I’ll link to it in the notes. The title of the paper is: Comparative analysis of phenolic acids and mistletoe plants from various hosts. The year is 2001, that this paper was published.

So yes, it was six trees. I have them here in my notes. The six trees, they pulled mistletoe from where? The Norway Maple, the Rowan tree, the Cottonwood Poplar tree, the European Pear tree, the Apple tree, and Yew, English Oak (Quercus robur). I may be saying that wrong. Quercus robur.  Or Quercus robur. That’s the English Oak, the English Oak tree that was so sacred to the Druids.

I was so happy. I pulled down the PDF of this paper and I have a closer look. What’s going on in here? They used chromatography to study the phenolic acids – which is only one of many active components in these mistletoe extracts. But it gave me an idea of how, the extracts might be so very different between different trees. And if you download this paper, again links in the notes, they have graph after graph about the different acids in each tree. And sure enough, they found big differences in the mistletoe extracts. One tree gave one mistletoe extract a phenolic acid that wasn’t found in any of the other mistletoe extracts and so on. It wasn’t very different, but none of the profiles matched each other exactly.

So the tree, the mistletoe plant grew on was in fact very, very important for my story. Could it be there was something special about the English Oak tree? I went hunting for English Oak trees in England, London specifically, that would be perhaps hosts for a mistletoe plant. Could there be one in Hyde park?

Sadly, I didn’t actually find an Oak tree in Hyde park with a mistletoe plant on. It turns out, as of the year 2000, there are only 11 Oak trees in all of Britain that had mistletoe growing on them. Most of these were found in Herefordshire. Sorry if I got that wrong. Herefordshire? So mistletoe growing in an Oak tree, very rare and very special. Maybe these companies producing mistletoe extract as an adjuvant therapy simply couldn’t use Oak trees because there weren’t enough of them to harvest to make their product? So they turned to Apple trees, with which they had the best results?

Mistletoe growing on Oak trees, something that’s rare and special. A plot was born. This is where my story turns very fictional in that age-old game an author plays: What if?  What if there was an English Oak tree known as the Druid Oak growing in Hyde park?

Thank you so much for listening. I hope you enjoyed hearing about mistletoe and how it made it into my story, A SNOWFLAKE AT MIDNIGHT. Next time on the podcast, I’ll talk about how the medieval manuscript made it into A SNOWFLAKE AT MIDNIGHT.