In this interview, Benton Bramwell, ND, discusses the unique Mediterranean herb Arum palaestinum. Listeners will learn about the traditional use of this herb, as well as current research that helps illuminate its modern-day clinical applications including oncology specifically. Synergy, safety, and dosage will also be discussed.
Approximate listening time: 31 minutes
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About the Expert
Benton Bramwell, ND, graduated from the National University of Naturopathic Medicine in 2002. He manages a private practice and also provides consulting services to food and dietary supplement industries in matters of scientific and regulatory affairs. He enjoys the wonderful outdoors, especially working the vegetable gardens with his family and going on bicycle rides that allow him to think and exercise at the same time.
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Karolyn Gazella: Hello. I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today, we're going to have an interesting discussion about the Mediterranean herb Arum palaestinum. My expert guest is Dr. Benton Bramwell. Before we begin, I'd like to thank the sponsor of this topic, Hyatt Life Sciences. Dr Bramwell, thank you for joining me.
Benton Bramwell, ND: Pleasure to be here, Karolyn.
Gazella: Well, let's start with the basics. Where does Arum palaestinum grow?
Bramwell: Great question. Arum palaestinum grows in the Mediterranean region and is particularly known and used in the Middle Eastern portion of the Mediterranean.
Gazella: Okay. Perfect.
Bramwell: Quite a history to it actually, Karolyn. It's been known in the region for actually, literally, thousands of years. In fact, it shows up on some drawings in ancient Egyptian temples. We believe it was probably brought to Egypt from Canaan in about 1440 BC. It's been there for a while.
Gazella: Yes. Yes. Also from a historical perspective, what conditions was it used traditionally for?
Bramwell: It appears from the historical literature that it's been used for many different kinds of conditions. Primarily for a treatment for cancer, historically, but also as a treatment for infections and open wounds, as a treatment for kidney stones, and even for a worm treatment in animals and humans. Also, it's a way to strengthen bones. This is one herb that has been used in a very diverse applications, perhaps not the least of which because it happens to also be a wonderful food. It made its way from food into medicine. Really that distinction as, of course, you know in a lot of places in the world, there really is no distinction, right? A lot of times the best medicines come from our feed. This is certainly a prime example of that.
Gazella: Yes, exactly. Let's fast forward to today. What are the main clinical applications of this botanical today?
Bramwell: Yes, we're still learning about that in terms of modern application, where it's going to be the best fit. We certainly continue to see it used clinically in the ways that has been used traditionally previously. That's in the Middle East. It's still used as a complimentary supportive adjunctive support for patients with cancer. It's also finding its way into skincare, and I think we're catching up, frankly, in the modern scientific age as to where it should be best used. I think we still have a lot to learn there, but we're learning as we go.
Gazella: That's a pretty diverse list of conditions that this herb can help with, which is kind of common with some botanicals. I'm assuming that's because there's a variety of mechanisms of action. Is that a correct assumption? Can you tell us exactly how this botanical works in the body?
Bramwell: Right. I can tell you what we're starting to see there and understand. There are a variety of mechanisms. Just for a minute, let's focus on where it might fit in terms of something that makes supportive sense for the patient with cancer. What we're seeing is that it may very well, at least in the in vitro models that we're seeing, it may very well help with the cellular process of apoptosis. That's the process by which a cell decides that it's time to basically do itself in. It's programmed cell death, right? There are some interesting mechanisms through proteins that are caspases. I think that we're going to continue to see the literature develop there quite a bit, but I think that's one important mechanism.
It's also important in terms of cell signaling by means of phosphorylation. There are many pathways in the cell which run off messenger systems based on phosphorylation. It seems that Arum palaestinum probably inhibits some of those pathways as well, or at least the compounds from. Those are several of the mechanisms that we see in play.
Gazella: Okay, good. I understand that there's a topical application of this plant. Can you tell us a little bit about the topical application and what that formulation actually looks like?
Bramwell: Yes, I can tell you a little bit about that. I'm glad to see that one coming forward. It's certainly in line with the traditional use. That product, Arumacil, it contains the Arum palaestinum extract, as well as dimethicone and petrolatum. The object there is to help protect the skin, give it a chance to heal, basically. I wouldn't be surprised, and I don't think the literature has necessarily caught up to us here, but one of the main categories of plant chemicals that we're talking about here are flavonoids. Flavonoids are known in the literature to have antiviral effects. Again, a little bit more to learn there, but I wouldn't be surprised at all to find this topical application of good use, clinically for people with cold sores and other minor skin irritations, frankly.
You're going to get a lot of antioxidant action from these compounds, as well as potentially some antiviral, although I think we need to learn more about them.
Gazella: Okay. That makes a lot of sense. From what I've read, this is a pretty complex botanical. It has a lot of different constituents. From the therapeutic perspective, what are some of the key active compounds in the plant?
Bramwell: Well, there are many actually. In the literature where I've spent some time, and from what we can find, there's about 180 phytochemicals that we can at least tentatively be identified at this point in time. Most of those, as I mentioned, are flavonoids of one kind or another. As I look at the list of what's been identified, some of those I would pull out would luteolin, which I think is going to prove to be very important from an anti-inflammatory point of view. That's certainly an active bioflavonoid, in particular, a class of flavonoids called flat bones. I think that's going to, doing the [inaudible 00:07:52] one of the important ones. But there are others as well. There are derivatives of rutin in there, and epicatechin. So I think those are all going to be important.
In addition to the flavonoids, there are also phenolic acids and derivatives of phenolic acids in here as well. Rosmarinic acid is one that pops out, and these are all compounds that I mentioning that when you look at the individual ingredient, it doesn't take you long to find in the literature that these individual ingredients, upwards of between 20 or 30 of them, have a little body of literature of their own, as to their anticarcinogenic potential.
And so, I think what we've got here among the flavonoids, the phenolic acids, and I should mention also some terpenoid derivatives, of course solic acids in there as well as some iridoid derivatives. When you put all those together, and each of them have an anticarcinogenic potential, the complexion of the botanical is one that seems well suited for its historical use.
Gazella: Yes. Especially when you consider a condition like cancer, which in and of itself is so complex. I'm fascinated by the fact that there are all these little compounds, and as you've mentioned, you could probably take one compound, do a scientific literature search and find data to support that one compound, but here we're talking about multiple compounds all within the same plant.
Bramwell: Well, that's exactly right. And actually some of the interesting work that's been done, one of the interesting approaches here is to take some of the compounds that occur in the plant naturally and make a fortified extract, if you will. So, that work's been done in vitro and in vivo and in several different places. They've taken out, for example, linolenic acid, beta sitosterol and isovanillin.
Those are items, constituents that you can get in a water extract of the plant and then made a fortified product from that... material. And when that material has been tested in the in vitro and animal models, it seems to perform superiorly to the raw extract, and I find that very interesting. It seems that Genzada Pharmaceuticals, Hyatt Life Sciences have done a very good job in the work that's been ongoing here showing an increased potential of this fortified extract approach.
Gazella: Yes, that sounds like some pretty cool science. I want to focus, in particular, on a 2018 study that was published in scientific reports. Now in that study, it compared to three different formulations and all of the formulations included Arum palaestinum. What were the results of that study? Tell us a little bit about that particular study and what the objective was and what the results were.
Bramwell: Right. So, this is an approach, again, where a fortified... a number of things were tested. One of the things that they tested was combination of the three plant extracts, Arum palaestinum, curcumin longa, which most people are familiar with turmeric, as well as another from the Middle East peganum harmala, sometimes known as Syrian rue.
So, those 3 botanicals were studied together and then various combinations of a fortified extract, or in one case, a chemical constituent from each of those was mixed together, and that actually looked the most potent as far as it's anticarcinogenic potential. And in that case, isovanillin, which you would find in the Arum palaestinum, was mixed with harmine, which you would find from the Syrian rue and also curcumin from the turmeric and all three of those plant chemicals were used together. And that actually seemed to have a very potent anticarcinogenic effect in the in vitro and in the animal models that we're studying here, in terms of looking at the invasive potential and proliferation, of the cancer cellulars models that we used.
And in this case, the researchers were looking at the head and neck squamous cell carcinoma, which is a very fast growing, aggressive kind of cancer. And, it does appear that the cells that were used here were very sensitive in these models, to that combination.
Gazella: So remind us, which combination then performed the best in this particular study?
Bramwell: Right. In this particular study, the combination of the three phytochemicals, so isovanillin, Arum palaestinum, and harming from the Syrian rue and curcumin from turmeric is what performed the best.
Gazella: Got it.
Bramwell: And again, they were able to show the effect on the molecular signaling cascades within the cell. So, there's some definite believable mechanisms of action here as to why the compounds would have the effect that they do. I think we're going to see a lot more about this one in the future as it becomes translated to human clinical studies.
Gazella: Right. Yes. Based on that study and other research, it sure seems like Arum palaestinum is best used in combination, potentially with other botanicals versus as a single botanical. Is that true? And if it is true, why is that?
Bramwell: That's an excellent question. I think that probably is the case, that either combination of the Arum palaestinium with other botanicals or even compounds, key compounds, from each of several important medicinal herbs. The question is why do we see this additive or even synergistic effect with these compounds or with the botanical blends that seems to manifest in the literature? I don't know all the reasons for that, but I rather think, given as complex as cancer is, being able to affect multiple pathways is probably the breadth of the attack against cancer cells, is probably why we're seeing that synergistic kind of benefit.
One way to attack something is with a very narrow focused approach. A deep attack. Another way is with a multitude of effects together. A nice, you know, cover all the bases. And I think that's potentially what we're seeing as this literature sort of declares itself here.
Gazella: And now what combination or what product, what Arum palaestinum product do you use in your clinical practice?
Bramwell: So right now what I'm using is the Afaya Plus and you can learn about that, consumers, patients, physicians can learn about that at the Hyatt Life Sciences website. But I think that that's the best product certainly than I've seen on the market at this point in time.
Gazella: Mm-hmm (affirmative) great. We'll also provide a link to the website too, so listeners can click right over. So, so far, there's been some compelling in vitro and in vivo and we all know that that's kind of the progression of research as we study these botanicals. What about human clinical trials?
Bramwell: That's the next step really, Karolyn, and I don't know when those are going to be published or what stage we're at, but we're definitely ripe for what would be called phase one and phase two clinical trials here. From what I can see in the literature.
Gazella: Are they underway? Phase one, is this phase one underway or is that still, are we still waiting for them?
Bramwell: I think we're still waiting for that, at this point in time. I hope to hear more about that in the near future. But at this point, following the literature and everything we see we like.
Bramwell: And can't wait for the next human work to actually be published.
Gazella: Yes, I mean, the traditional use combined with the preliminary research sure does seem to be compelling. I'd like to talk a little bit about how it's used in oncology in particular. Do you look at this botanical as an adjuvant to be used with treatment or maybe after treatment? What's the clinical application when it comes to oncology?
Bramwell: Right. Well that's a very good question and because of where we are in the scientific process here, we're still early on. Although I think Hyatt Life Sciences, to be fair, has done much more work than many dietary supplement companies ever do. But we're not there yet in terms of knowing all we want to know. So at this point in time, I don't think anyone would responsibly say that this is a treatment for cancer. What we would say is, traditionally the syrup has been used by patients who have cancer. It's part of our herbal armamentarium historically, and it seems to make supportive sense.
And so, this would be something I would recommend while the patient is going through treatment. Although I tend to leave a space of time between conventional care and herbal therapies, just to make sure that the chemotherapy has time to do its work. So I would tend to leave three or four days, or at least one or two before and after a chemotherapy treatment. I think, from what I see in the literature, at least from the the Middle Eastern region where this is used quite heavily, when oncologists in that area are surveyed, they're not reporting anything really of concern as far as interactions go. But I would still leave a couple of days on either side of treatment, make sure the chemo gets in and does its job.
Gazella: Yes, that, Oh, go ahead.
Bramwell: No, you're fine.
Gazella: Well, I think that that's a good, prudent recommendation and I think that oncologists would agree with that. Now beyond oncology, is the herb safe? You talked about no interactions with chemotherapy that we know of, but are there any other interactions or contraindications that we should know about?
Bramwell: You know, not that we can see at this point in time. The only thing I would point out and highlight there, Karolyn, is that even in traditional use, where this has been used as a food, what's been known for a long time is that it's boiled. It's boiled several times in water and that water is decanted several times, taken off, in the preparation of the herb as a food. Or in this case, before it's a supplement. Don't know all the reasons for that, but part of the thinking has been there that there's a high amount of oxalates in the plant and in order to prevent toxicity, that's an important part of the plants preparation as a food/medicine. So, I would highlight that for you.
Gazella: Yes, that's interesting. Is there any kind of standardization with this botanical?
Bramwell: Yes, it could be standardized. But since we're in the process of learning all that's important about it, I think the closest thing to standardization is the work that was done several years ago with the fortified extract of isovanillin, linolenic acid and beta sitosterol . That complex looked quite promising. And if you wanted to standardize to something, that would be one way to do it, but I'm not aware of a totally standardized extract at this point without fortification, if that makes sense.
Gazella: Okay. Yes. Let's talk a little bit about dosage. So what dosage do you recommend and does that dosage change based on the clinical application or if it's for prevention versus treatment?
Bramwell: I would tend to be more aggressive with a patient who's using this as a supportive. Make it a supportive care during cancer. And the Afaya Plus, two capsules [inaudible 00:23:07] of that is going to give about 900 milligrams, of a combination of vanillin powder, tumeric powder, harmala powder, the Syrian rue and Arum palaestinum. I would tend to go at least two capsules, twice a day on that.
But again, when you're working with a patient with cancer, you're going to have to titrate the need, titrate the dosage that they can take. Some patients going through treatment have a difficult time getting food in. And one thing we always have to remember with a patient with cancer is that we want to feed them first. And we don't want capsules to take the place of food, and so it's going to depend on what the patient can tolerate. But I would start off with a two capsule b.i.d. kind of an approach. And if they can tolerate that well, even up to two capsules t.i.d. As a maintenance kind of thing, for general health, I could see taking a single or two capsules a day, single serving.
Gazella: Do you feel like it has a good application? Like for example, somebody, a patient who may be at high risk of developing a type of cancer. So as a way to kind of help reduce risk, do you feel like there's an application for that?
Bramwell: We don't really know at this point, but I would suspect so. There again, I'm not one to, I don't necessarily subscribe to the philosophy of more is always better. But I think it's something that I would carry in my mind. You know, if dad and grandfather both had prostate cancer and I want to take something and it's kind of a daily maintenance to keep as healthy as I can, to maintain that prostate tissue in a good state, I would think of serving of this a day would make a lot of sense.
Gazella: Okay, great. Now, we talked a lot about oncology, but we also mentioned skincare, infections, kidneys, bones, when you're looking at the clinical potential of this botanical and the clinical application of this botanical, does oncology bubble to the top over everything else?
Bramwell: I think it definitely does. In fact, there are many other applications that we've mentioned here. And we're going to learn more about those over time. I think this is something that naturopathic physicians and other integrated healthcare practitioners are going to learn about as they go. And that's okay, really. We're using something that's been in traditional use for a very long time. But it would be something that for other conditions like skincare, I would just try it clinically and see what we see with it. But I think the biggest, biggest application, Karolyn, is going to be oncology.
Gazella: Yes, I would agree based on what we've discussed today. For sure. Now, Bramwell, I'd like you to pull out your crystal ball and kind of look into the future as a clinician, what would you like to see happen with this botanical as it relates to oncology specifically?
Bramwell: Couple of things and I think already some progress has been made in terms of what formulations are the most effective, but I'd like to see a little bit more work in that regard, with various combinations. I think that we will see, in the next few years, based on what's already been done, phase one and phase two clinical trials. And I hope, based on what's done that that includes work in both patients with prostate cancer, as well as patients with head and neck squamous cell carcinoma and some of the other lines that have shown promise. I mean, there's been some work that's a promising in glioblastoma cell lines as well as lung cancer. So we'll see where it goes in humans first, I hope with patients with prostate cancer and patients with the head neck cancer especially. I also am intrigued, in that 2018 paper that you referenced, there was some work indicating that it may go very well in combination with Cisplatin.
Bramwell: Platinum chemotherapy is very commonly used in colon cancer treatment, as well as other cancers. And boy, if there would be something that would help the platinum chemotherapy be even more effective than it is, I think that would be a wonderful combination and as I kind of look to the future, that one comes to the front of my mind, Karolyn is, is this an adjunctive therapy that could actually make the conventional therapy a little more effective? And I would really hope that the future upcoming human work will really hone in on that and help to answer that question.
Gazella: Yes, and it would also be kind of interesting to see if this botanical could help reduce some of the side effects that come with conventional chemotherapy. I think that would be kind of an interesting... I'm curious as to why prostate and head and neck. I mean, head and neck, that's a tough one and I would love to see it be effective, but why are those two ones kind of standing out in your mind as to where this botanical may help?
Bramwell: Right. Well that's based on the work that's been done so far. So yes, there's going to be a great, great question. The 2018 work was primarily done in head and neck squamous cell carcinoma, and the work before that, in 2015 that was published, was quite focused on prostate cancer cells. So, it makes sense to build on what you have there.
But, you know what? Here's the great thing about Arum palaestinum, from everything I'm reading, it looks like the mechanisms of action, and there are multiple of them, could be applicable across many kinds of solid tumors. So this would be the kind of thing where you can build on your in vitro and animal work and human studies, but you might quickly branch out and other areas of exploration as well. It could be something that could be beneficial to many patients. We don't know yet, I don't think. But, when I read this literature, the question I asked myself is, could this be the next [00:30:30] ? Could Arum palaestinum be that botanical source for a cocktail of phytochemicals that really finds broader use and helps many patients live longer and much better lives. I hope so. Time will tell. Human data will certainly inform things from here, but what we see so far is it's highly encouraging and kudos to the Hyatt Life Sciences for getting this out there.
Gazella: Yes, I hope so as well. It sure sounds like there's a lot of potential here and we're going to definitely, The Natural Medicine Journal, will definitely be following this research on this interesting botanical, Arum palaestinum. Well, once again, thank you Bramwell, for joining me today and I'd also like to thank the sponsor of this topic, Hyatt Life Sciences. So, thank you for the interesting information, Bramwell, and I hope you have a great day.
Bramwell: Well, thank you, Karolyn. Pleasure to be with you.