Mistletoe In Integrative Oncology: Uncover Its Immunologic Benefits

Steven Johnson, DO

Thank you for having me.

Michael Karlfeldt, ND, PhD

For all the viewers, Steven Johnson was the chief resident of internal medicine at the University of Massachusetts-affiliated hospitals in Worcester in 1996. He has taught frequently in Europe and the US on integrative medicine, oncology, pharmacy, anthroposophic, biological, botanical, and nutritional modalities. Dr. Johnson directed one of the first major integrative medicine clinics in the United States, bringing together a multidisciplinary team with extensive conventional and holistic modalities of care. He has spent the majority of his career deeply immersed in clinical practice, helping patients across the country with oncological, autoimmune, and challenging degenerative illnesses. Dr. Johnson has written numerous magazine articles, been a guest on several radio shows and podcasts, is a coauthor and project editor of the new book, which I have on my show, which is incredible Mistletoe and the Future of Integrative Oncology, has written and published several small educational books on homeopathic and botanical medicine, is a well-known consultant for Integrative Pharmacy, and has formulated numerous botanical and holistic medicines used internationally, as well as assisted in the development of extensive botanical gardens for pharmacy production. Recently, Dr. Johnson has been the director of the first European Mistletoe Integrative Oncology Training Program and serves as a mentor to clinicians across the country. He has served as president of the Physicians Association for Anthroposophics and is the founder of the Foundation for Health Creation to promote resilience in our challenging times. He’ll be launching a new resilience course for patients and practitioners soon. He is also the medical director of the Camphill Village Medical Clinic for Adults with Developmental Disabilities and runs a part-time private consulting practice. He is active as a strong advocate for an integrative model of health care and public health in North America. You’ve done a lot. You are doing a lot. How do you have time?

Steven Johnson, DO

Yes, that sounds like a lot. 

Michael Karlfeldt, ND, PhD

That was a mouthful.

Steven Johnson, DO

Yes. I guess as you get into your sixties, a lot of time has passed.

Michael Karlfeldt, ND, PhD

One of the therapies that is in one of your latest books on mistletoe and is such a powerful therapy is something that I do here at the center. Tell me a little bit about how you came to know Mistletoe and why that connected with you.

Steven Johnson, DO

Yes, I had an interest, as you could tell from my biography in Plant Medicine. I had always been very interested in botanical medicine, and I met Mistletoe, particularly through anthroposophic medicine. I know that is a mouthful of anthroposophic medicine, but in Western Europe, it is the form of medicine around which whole clinics and hospitals have been built, where both integrative modalities and conventional modalities of care are given, including in oncology, and Mistletoe is used in those settings. I had the opportunity in my training, even as a resident, to go over and spend some time in those hospitals. I could see it being used adjunctively early in modern oncology, and I was very impressed at that time. It made an impression on me, such that later I got more involved in that kind of care for myself.

Michael Karlfeldt, ND, PhD

We’re going to go into Mistletoe quite a bit and, in a moment, explain to me the anthroposophic. What is that? What is the kind of mindset?

Steven Johnson, DO

It is a small movement in a way that is done a lot. There are three large pharmacies around it in Europe and across the world. There are many hospitals and clinics in Europe. But the main thing that separates anthroposophic integrative medicine from other modalities is its constant search to humanize medicine, to recognize that there’s something of a higher spiritual nature to healing and health, as well as scientific. Similar to the old traditional medicines like Chinese medicine and Ayurvedic medicine, there’s a deep constitutional and spiritual approach to healing, a way of looking at the human being that facilitates a more intuitive way of practicing that should be verifiable scientifically, but it takes a certain training to develop that sort of intuitive capacity to work with plants and different illness processes, minerals, nutrition, and how they relate to different, I would say, illness and health processes in human beings.

Michael Karlfeldt, ND, PhD

I know mistletoe plays a role in that, and I know in regards to where it is grown, what type of tree it is, and when it is harvested. There is a lot more to it in regards to mistletoe than just, I hear mistletoe and take it and it will help you. There’s a whole process of understanding which one is best for which individual and in what state. It is fascinating how those two come together. You mentioned that mistletoe is more commonly used in Europe, and that is almost like a care that is right along with traditional oncology as well. Was I hearing you right there?

Steven Johnson, DO

I don’t know if it would be fair to say it is in every oncology center in Europe, but there are whole hospitals and centers, several of them in Europe, that do bring those together. That is very unique.

Michael Karlfeldt, ND, PhD

Tell me about mistletoe, what it is, and how that would benefit an individual battling cancer.

Steven Johnson, DO

Sure.  First of all, mistletoe is such an unusual plant. When people read about it, their eyes open up with a sense of wonder. You have this almost ancient plant that is parasitic. It grows on other trees and doesn’t harm them. One of the most unique properties of mistletoe is that it blossoms and flowers in the winter, not in the summer. It has its unique rhythm. You could say it is a strong individual body of its own. If we think of that as a metaphor, before we get maybe more into the scientific side of it, that is a little bit of how we sometimes look at mistletoe from a holistic standpoint. It strengthens the individual’s capacity and makes the individual stronger in their immune capacity and the capacity of their body to recognize something like a tumor or something abnormal and harness the immune system to become more active around it. You could say I like to use the word immune surveillance, which is heightened by the mistletoe.

Michael Karlfeldt, ND, PhD

It is almost because a person dealing with cancer is obviously in a weak state. When you think of the winter, you think of when the energy is low, and that is when it is the most powerful. That is when it is blossoming. It is almost like that when it steps in when the body is in a weak state.

Steven Johnson, DO

One of the beauties of using mistletoe is that it can be used in all stages of cancer or all stages of an illness. We may choose a different host tree—a tree on which the mistletoe is grown. If we want to support more vitality or if we want to be more aggressive immunologically, then we may choose a different tree. But in general, patients feel better on mistletoe, and if they don’t feel better or more resilient than before they took it, usually it means some type of subtle change is needed, as is the type of mistletoe or the way it is given.

Michael Karlfeldt, ND, PhD

How would a practitioner then choose the form you mentioned depending on an individual’s act and journey? What kinds of trees are commonly used, and what does each tree contribute to the qualities of mistletoe?

Steven Johnson, DO

That is such a fascinating question. It can be answered in two ways. It can be answered the way a traditional medicine practitioner might answer that question and the way an academic, conventional scientific person might answer that question. There are two sides. We know that when mistletoe is grown on different host trees, there are oaks, apple ash trees, popular poplar trees, birch trees, and hawthorn trees. There are several we could talk about. But what we note is that when we test the preparation and the extract, there are different levels of the active constituents in those extracts from different host trees. Through various studies over the years, we found that different types of mistletoe work better with certain types of cancer, like, let’s say, a molly grown on an apple tree. Mistletoe growing on an apple tree might be better for reproductive organs, or Quercus and oak trees might be better for digestive organs. In that sense, we could show that in significant hospital studies, some of them with many patients, not all even small studies, and then there’s the other side, where maybe, like a homeopath or a traditional medicine practitioner, we look more at the constitutional aspect of the person.

How is their vitality? Have they been traumatized? Are they going through a depression? How is their overall health? What’s their personality like? Are they workaholics who do everything for everyone and nothing for themselves? That would be a Quercus-type person. For instance? Or is it a person who has given a lot to their children or is constantly in service of others but doesn’t get the support that they need? That might be more of an apple-tree-type person or constitution. It is a bit simplistic here, but there’s this kind of picture that you can form that relates to the host tree that we’re using. I would say practitioners who have used it for a long time are usually turning to a bit of both in how they look at it. Some practitioners are more comfortable with one approach than the other, but both exist and are used around the world.

Michael Karlfeldt, ND, PhD

So you’ve talked about mistletoe and how it can increase the vitality of an individual. What are some kinds of scientific studies regarding what mistletoe can do for an individual immunologically?

Steven Johnson, DO

Yes, I think there are two parts to your question. But, correct me if I didn’t understand it correctly, the majority of the best studies on mistletoe are on quality of life. Parameters like vitality, energy, appetite, sometimes less pain, improved mood, and improved sleep—these qualitative aspects run alongside the mistletoe treatment for cancer or the disease we’re using it for. Sometimes we’re using it for other things, like long COVIDs and things like that. then there’s also the side where mistletoe can be that the type of host tree we choose can be supportive of the vitality. If we use pine mistletoe in someone who is very weak and depleted, maybe after chemotherapy, for instance, or has lost a lot of weight, then it can help someone who’s kept it very weak with a poor appetite to build that backup as it is helping to treat the disease. then maybe later on, when they’re stronger, we might use a stronger mistletoe that has more, I would say active constituents that rev up the immune system towards cancer, such as lectins, and mistletoe lectins are the most common thing we study, and very high lectin preparations of mistletoe like the fraxinus, which is an ash tree or a Quercus, and oak trees tend to be very high in lectins, which we might use in a more aggressive tumor or tumor that is metastasizing, are things like that. Maybe we should use something from a fir tree or a pine tree that has fewer lectins in it, but it can still stimulate immune surveillance quite well.

We might say that the patient is a bit weaker, and the higher lectin preparations also lead to more apoptosis in the tumors. They can weaken the cell walls of tumor cells. They can help with genetic and DNA repair. There are many aspects to these mistletoe lectins. The list itself would take an hour to discuss. then there are other constituents there too. Like this, toxins, which are like snake venoms or similar to venoms, antioxidants, and other glycoproteins that we know are beneficial to cancer patients, both preventatively and in treatment, make it quite a dynamic plant in that way. There are over 12 or 13 different pathways of immune regulation toward tumors that exist in the mistletoe plant.

Michael Karlfeldt, ND, PhD

Then we have the topic of hypothermia, where you use a fever to trigger an immune response like a fever to support the body to kill off cancer cells. I know mistletoe can play a role in that process as well.

Steven Johnson, DO

Some people get fevers from the different preparations, as practitioners understand the different preparations of mistletoe better. They can sometimes stimulate a fever. It is more difficult to stimulate fevers in the modern patient, I think than in the patients when mistletoe, the patients to whom it was first given. I think we can see that the average temperature of the human being is coming down, and it is harder and harder to trigger a fever. For many of our patients who have cancer, if you ask them, “When’s the last time you had a febrile illness?” They’ll say, “I can’t even remember.” But there are methods by which we can use the mistletoe to raise the temperature very mildly and gently. If we start slow and build it up, we might get a very small temperature increase of a few tenths of a degree. then there are techniques for advancing it quite rapidly with both subcutaneous and IV at the same time, giving very high doses right from the start. This might cause some strong skin reactions and a little discomfort at first, but no one’s ever gotten very sick or died from mistletoe getting a fever. In those cases, some people get a little bit more of a fever, which is temporary, lasting just a few hours, and then it usually comes down. A slight temperature increase is often associated with better outcomes, but it depends on the patient and how fast you can do that. how much, and also the type of mistletoe we use. Is that helpful? I don’t know if I fully answered your question.

Michael Karlfeldt, ND, PhD

No, that is perfect. You are doing great. Talk to me a little bit because a lot of people in their daily lives become afraid of fevers, and they try to do everything they can to stop fevers themselves. children as well. Talk a little bit about the benefits of fever overall—not just cancer, but overall.

Steven Johnson, DO

That is a great question that would be a great topic for a whole conference in itself, I think. I believe that you can statistically observe that the increase in chronic disease in our civilization is also connected to fewer fevers and fewer febrile illnesses. If I think back to my first mentors, who were primary care doctors, the most common things they saw were acute abdominal illnesses with high fever, scarlet fever with high fever, lots of strep throat, and all kinds of rashes. We still see them, but nothing like we used to when we were young kids. We’re seeing the chronic illnesses that we expect in the forties, fifties, and sixties, starting earlier and earlier in life. Many of us believe it is because people don’t have proper illnesses. They haven’t strengthened their immune system and gone through the process of building up their antibodies. to different foreign invaders, infections, and things like that that strengthen the immune system, the immune process in us is connected with fever. If I could use one difficult word, it is salutogenic. Salutogenesis means the origin of health. Whereas pathogenesis, the word we mostly use in modern medicine, means the origin of illness. A fever generates health—a healthy fever.

I’m not going to say you let somebody get a fever of 105 and get a seizure and pneumonia. No, but immediately suppressing every small fever with Tylenol and Motrin may not be the best thing because if a person is followed carefully and gets the right kind of supportive care and they have a few days of mild to moderate fever, they usually get through the illness more resiliently than before. If you have an earache, your kids are much less likely to get a lot of your aches if they get through one on their own. Or we can become strengthened by a fever. If what I’m trying to say is in its proper place, is that a fair thing to say? Yes, I see that in my practice and over the years. I think it is one of the most important questions that could be asked.

Michael Karlfeldt, ND, PhD

Who was it that said, “Give me a fever, and I can cure anything?”

Steven Johnson, DO

Yes, I can’t remember. 

Michael Karlfeldt, ND, PhD

I’m trying to remember, but yes. I see the same thing. Because the fever activates the immune system, there’s higher immune system involvement and greater antibody production. Also, there’s a cleaning of the house, where you burn up debris, viruses, and pathogens. They’re broken down. The immune system can kind of see these small components and then develop the appropriate antibodies. So it is a fantastic event for the training of the immune system. like spring cleaning.

Steven Johnson, DO

I think you are correct. I see the same thing. One short example I often like to give is that if you are a parent and you can remember your children when they were young going through a fever, I noticed in my children that often they would seem different. After that fever, they might even look a little different, and their color changes and something seems to have been, like you said, cleaned out and sort of reborn a little bit. In a healthy, controlled fever, you can see a strengthening and vitalization of the organism. But I think it is fair. We both have to say it has to be watched. We’re not. One wouldn’t want to say you let all fevers run rampant. That is not what’s being said here.

Michael Karlfeldt, ND, PhD

A lot of the therapies, holistic therapies, lean on things like hypothermia in regards to cancer, as well as recognizing the importance of a fever to be able to control even something as advanced as cancer cells.

Steven Johnson, DO

There are studies with leukemia lymphomas where, after pneumonia with a high fever or a near-septic reaction, there was a remission or reduction in the tumor burden. We have seen that. But how to control that is still a question. All these new immunotherapies are coming out, and mistletoe was the first immunotherapy, you could say. Now we’re trying to create new immunotherapies synthetically. I think the verdict is still out on how well those are going to work.

Michael Karlfeldt, ND, PhD

Yes.  The power of using something herbal like mistletoe versus a chemical version is that it is complex and also works with the body’s innate intelligence, so it is not going to dis-regulate the body. It is always going to be supportive and leave the body stronger than it was before.

Steven Johnson, DO

I just want to mention that that is true: 99% of the time, you can give too much mistletoe and make it cytotoxic. But if it is given in the right way, everything you say is true. I think that maybe magic is not the right word. But one of the wonderful things about mistletoe is that it is a medicine and that it plays well with other therapies. There are very few contraindications where you can’t combine mistletoe with another nutritional, integrative, or conventional treatment. There are very few situations where you can’t use them together. Over the last eight years, that mistletoe has been in existence. Of course, it is getting better and better every decade and more refined, and the production methods are getting better and better. There are still only a handful of reactions ever reported over all those years with other medications.

Michael Karlfeldt, ND, PhD

What are some of the kinds of things to watch out for in regards to mistletoe? Are there times when you should not do it? Are there concerns regarding mistletoe? You mentioned 99.9. What are some of the times that it may not be appropriate?

Steven Johnson, DO

There are a few instances where you wouldn’t want to give mistletoe, or you’d have to wait. The most obvious would be an infection. If you have an acute infection with a fever, you don’t give mistletoe at that time. You wait until it is over. You wouldn’t give it during a pneumonia or a bladder infection or sepsis or something like that, because we don’t want to heighten the immune system, that is all, and make it overstimulated. That would be a big mistake. We stopped it during that time. If someone’s in an acute autoimmune phase, let’s say with acute colitis, hypothyroidism, or an acute flare of lupus, the way it regulates the immune system might heighten some aspects of that autoimmune response. In those acute phases, we want to use it very judiciously, at a low dose or not at all, unless it is under control. chronic phases where people are stable, we don’t worry, but that would be one of the main areas, and then allergy, and there are very few instances of allergy to mistletoe. If you studied and trained more in it, you would go more into that. But there are very few metabolic conditions where you can’t take mistletoe. But there are a few. 

Michael Karlfeldt, ND, PhD

How is that administered? What would a treatment protocol look like for those who are interested?

Steven Johnson, DO

The most common is SUBQ, which is an injection like an insulin shot for diabetics. Very teeny, tiny needle. You can use almost the smallest one you can get, and you can inject it subcutaneously into the skin. A lot of people want to know: Can we use it orally? You can use it orally, but there’s still no study that shows that you get high enough levels of lectin, viscotoxin, and other constituents to come close to the injection. Maybe we would use that with a child or someone who absolutely couldn’t take it. Then IV is the next most common intravenously, where quite high doses can be used of mistletoe, much higher than subcutaneous. We usually use that in the more acute phases of cancer or the early phases of treatment. In Europe, for instance, mistletoe is injected directly into tumors. It is used for pleurodesis in the lungs with fluid or sides in the abdomen. Those kinds of things can’t be done so much in the United States because they usually have to be done in a hospital. But it has even been injected that way. Yes, in different parts of the world. Mistletoe is growing a lot right now in East Asia and South America as well. Many, many doctors are starting to use it in clinics in those places, almost more than in Europe now.

Michael Karlfeldt, ND, PhD

With the subcutaneous injection, is that a daily thing that you just do a certain dosage and stick with that dosage? how long of a treatment phase?

Steven Johnson, DO

I would say the average is three times a week. That would be an average number of times the mistletoe is given a week. Whether it be IV, SUBQ, or a combination, there are times when people have used it daily or every other day. You have to be careful about how much you use and for how long. But that is possible. In cases where the cancer is in remission or we’re using it more prophylactically than some people, just take it one or two times a week with pauses during the year to kind of support the immune system and kind of a rhythm. Someone might take it a month on, a month off, or take it for a month and then take it for two weeks. Or if you are long-term in remission, maybe you just go through a cycle four times a year. There are many possibilities for the rhythm, but I would say three times a week is the most common.

Michael Karlfeldt, ND, PhD

How do you know what kind of dosage to do when you do SUBQ? You just kind of start at a certain dose and think that that is right. Or how do you approach the appropriate dose?

Steven Johnson, DO

I couldn’t teach a physician in this short time exactly how to do that because the actual milligram amount that you would start with is quite different for the different brands of mistletoe. There are several brands—four main ones—that are used in this country or in other countries too, and they have different lectin contents and different active constituent levels. Let’s say the most common one in this country is similar to what’s called Helix in Europe, and that we can build up pretty fast. You might start at one milligram, and then your goal might be to get up to 50 or higher milligrams in a few weeks. It could be that you react at five or ten milligrams and have to stay there for several weeks, maybe even a couple of months sometimes. I would say it is a process of escalation, whichever type we use. Many of the mistletoes come in escalation packs where they are escalating on their own, and you are just sort of following that escalation along. Then, when you get up to the right dose that you need, we give a more consistent dose of the same right, but we go by the skin reaction. Usually, we’re looking, especially in the beginning, for a little bit of a red dendritic reaction on the skin. We usually want it a quarter size or smaller, or if we’re getting about that much reaction, that is a good dose. As soon as that is reduced, we continue up. If we want to push it more quickly, we might say a silver dollar or a red reaction like that. But we use that red reaction, especially in the beginning, to guide how fast we can escalate the dose. That is the most common way we know. then by how the patient feels, how they feel, they feel healthy. So through these aspects of quality of life, we discussed engagement. Do they feel more vital in that way than we know we’re doing it the right way? Usually, if we’re not, the patient doesn’t feel good. They feel like they have the flu, maybe. Or they’re feeling a bit overburdened. Then we know we have to do it a little differently, but it still has never hurt somebody. I think there’ve been two selected cases in 75 years.

Michael Karlfeldt, ND, PhD

That is a pretty safe medicine, considering I’m sure there have been millions of doses administered during this time.

Steven Johnson, DO

Yes.

Michael Karlfeldt, ND, PhD

Are there some stories? And people always want to hear: What are some things that you’ve seen with mistletoe that have impacted this individual? And how did that turn out?

Steven Johnson, DO

Yes, sure.  With mistletoe in cancer and any treatment, we all know that can be a challenging disease. It can’t cure everyone. then wonderful things can also happen. If I were to choose one of my favorite cases, I would say it was one of those in-between instances where I had a patient with stage 4 prostate cancer. I think I put this story in the book because he was one of my close patients, and he was just given a month or two to live. It was already metastasized to bones and liver near the brain and in the lungs, and he said, Just keep me alive long enough to go visit these three churches of the Mother Mary. He wanted to visit Europe. We engaged him in integrative support of treatment with mistletoe, sort of at the core. He made it to those three churches, where he lived for six years. In that instance, with some spot radiation once or twice for a bone lesion, but otherwise he wouldn’t accept chemotherapy, which in that case has a very poor track record anyway for prostate that metastasized as stage four prostate cancer. But not just the cancer getting better and holding back for that period. I also noticed how active he was, how vital he was, and how positive his mood was. He had an extremely high quality of life with his wife and his children, and stories like that sometimes stick with me as much as a full remission, which is what we always want. We have many instances where mistletoe is part of that, too. Yes, but sometimes these kinds of stories where you see the dignity and strength of a human being shine through—you just don’t ever forget that.

Michael Karlfeldt, ND, PhD

How much is that experience worth? To be able to have those extra six years, to be able to achieve that goal in your life, and then to be able to transition knowing that you’ve done that and feeling complete—what a blessing!

Steven Johnson, DO

Then we have cases where, as part of the integrative modality, people, of course, got into remission. then there are some instances where it is either too far, too long, or too aggressive cancer, and mistletoe is not enough, and something else is needed. But for most cancers, it can play a positive role, I would say.

Michael Karlfeldt, ND, PhD

You mentioned a little bit about injecting into the tumor, and that is not done much here in the United States but more in Europe. What kind of benefit do they see there? Do they do that along with other types of therapies? What happens? What kind of impact does it have on the tumor directly by injecting it?

Steven Johnson, DO

There are a few studies out there and not a lot of intratumoral injections. It is done more in Europe. It is true. It is not approved to do it that way here. You have to do that out of the normal sort of FDA boundaries there and decide I’m just going to do it because my patient’s in a late stage of cancer or a difficult situation, and then we are allowed to give those kinds of treatments. I think there are some tumors that, let’s say, are locally difficult to move, or the person can have surgery for a certain reason, or a person can’t take chemotherapy right away for a certain reason. We can see a shrinkage, let’s say, of a breast tumor or a Merkel cell, which is one of the common ones. That is a rare tumor that responds well. enter tumor early in the studies in Europe and then SUBQ and prevent it from coming back. Lymph nodes, or a localized lesion, can sometimes respond to mistletoe and shrink significantly. But I would say that doctors should be very well trained if they’re going to do something like that.

Michael Karlfeldt, ND, PhD

Is there anything else that you feel should be covered regarding mistletoe for our viewers?

Steven Johnson, DO

I think mistletoe symbolizes something very important. It, I think, symbolizes where most of us who practice holistic and integrative medicine are trying to get. That is, to understand this word I said earlier, salutogenesis. How do we activate the body’s capacity to self-heal to the maximum degree? Mistletoe is not the only treatment that does that, but it very much embodies that in the sense that it can activate the immune system in a difficult situation like cancer and still improve quality of life at the same time when most of the medicines we would use in this case would make people feel sicker and less well. I think knowing mistletoe has been around for almost 100 years now. In the last 20–30 years, we have published over 100 new studies and research papers on mistletoe. I think it is a goal to shoot for. Why can’t we have more medicines and more approaches like that? Not trying to replace modern medicine. It has its place, and it is needed. But if we could reduce morbidities, make people feel better, and cure illnesses with so many fewer side effects, and also consider the combinations of all these medicines and the side effects they create when they’re combined, I think mistletoe is kind of a symbol of what’s possible, and I don’t mean that in a way to be rude to other approaches to healing because that exists in other modalities as well. But I think that just because it is cancer, mistletoe kind of shines a little bit. Hey, this is possible even in this situation. I think that part is special.

Michael Karlfeldt, ND, PhD

Well, thank you, Dr. Johnson. This has been wonderful. I appreciate the work you are doing and the education that you are bringing forth. Thank you so much.

Steven Johnson, DO

I appreciate you having me on. Blessings. Thank you.