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#30 – Supplements That Battle Covid-19, Repurposing Pharmaceuticals, The Cytokine Storm, And Getting Smarter For The Second Wave With Dr. Theoharis Theoharides

With the prospect of a universally effective vaccine in doubt, many of us have turned to diet and lifestyle to “shore up our Covid-19 defenses.” While many of the supplement regimens marketed as cure alls for Covid-19 are lacking scientific validation, natural compounds like vitamin D are showing some promise in serious research settings. What other nutrients can battle Covid-19? Are there pharmaceutical drugs that can be repurposed to assist in treating the coronavirus? Our guest today, Dr. Theoharis Theoharides has some answers. Dr. Theoharides is an MD, and member of the faculty at Tufts Medical School, who also holds a PhD in pharmacology, and a master’s in immunology, from Yale. We discuss the latest research on how flavonoids and other natural compounds impact the immune system and why this research matters for our approach to treating Covid-19 in the coming months.

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This Episode Covers:

  • The best hand hygiene techniques for Covid-19 [7:30];
  • Why Dr. Theoharides is a proponent of mixing quercetin and luteolin [15:00];
  • Molecules that can bind preferentially to the ACE-2 receptor [20:00];
  • The problem of patents in Covid-19 therapeutics [30:00];
  • Breaking down Dr. Theoharides favorite supplements for Covid-19 [34:00];
  • Taking precautions in preparation for lack of a vaccine [53:00];
  • How we study virus’ [1:01]


Voiceover: And I said, “Wouldn’t it be wonderful if they were to take luteolin, or quercetin and luteolin, and put it into, basically, something that I can spray in the mouth?” I mean, we have such sprays for asthma galore. Not with flavonoids, but with other drugs. So why couldn’t we just do an inhaler with these molecules, in which case, we deliver much of what we want directly to the lungs, no problem with absorption whatsoever? And we would get it right where the action is, as well. And no one seems to be interested, because there are no blasted patents.

John: Welcome to the “GeneFood Podcast.” I’m your host, John O’Connor. Hey, everybody. Today, I have a great episode for you that I think you’re going to enjoy. In fact, in the time I’ve been doing this podcast, the episode that we recorded here on this topic is…might be my favorite one that we ever done. Our guest today is Dr. Theoharides. He is a quadruple Yale graduate, he has an M.D. from Yale, he holds a PhD in pharmacology from Yale, and he also has a master’s in immunology from Yale.

He is currently a professor on the faculty at Tuff’s University Medical School, where he teaches immunology. And Dr. Theoharides is one of the world’s leading researchers on mast cells and the immune system. Some of you who listen to this show regularly will remember, about six months back, we had on Dr. Theoharides to discuss mast cells, histamine. And I wanted to have Dr. Theoharides back on the show, because I don’t think there’s anybody better to discuss some of the issues that our community is curious about, when it comes to COVID-19.

And one of the things that people want to know is, are there natural substances that can help with COVID-19? In short, do supplements help with COVID-19? Can I take vitamin D, can I take zinc, can I take quercetin, can I take vitamin C? The problem that I have with a lot of these natural-supplement discussions surrounding COVID-19 is… At least from where I’m sitting, it seems as though the commotion tends to lead, and the science tends to follow in its wake.

And what I like about Dr. Theoharides, as somebody who advises the Italian government on which outside grants to issue, somebody who’s published hundreds, if not thousands, of research papers on these issues, he has his finger on the pulse of the cytokine storm, because cytokines come from mast cells. The mast cells are a part of the immune system that releases these cytokines that we’re concerned with in severe COVID cases. But he’s also somebody who is not scared to test natural compounds, because of his background in pharmacology. He brings a unique perspective on these issues that I think you at home are going to find valuable. I’ve found my conversation with him tremendously valuable.

We get into topics like…as we’ve alluded to, supplements and COVID, put simply. We get into better policy for COVID, moving forward. How can we get smarter about COVID, tactical tips for how to clean your hands, how to do better with hygiene for COVID, pharmaceutical agents that could be repurposed for better outcomes with COVID. But the meat of the conversation centers around the ACE-2 receptor, which is the way that COVID-19 gets into the lungs, and different nutraceutical agents, different natural supplemental agents that we can use, potentially, to improve the immune system’s reaction, to maybe blunt the blunt the cytokine storm.

Now, we’re not here to say that if you’re drinking six beers a day, and you’re suffering from some comorbidity, some chronic condition that puts you at risk for COVID, that popping a supplement pill is going to solve your problems, because we all know that that’s not true. But there is serious research being done on this front. And we’re really just grateful and lucky to have somebody with the level of expertise that Dr. Theoharides brings to the table, to give us a tour through the real science on nutraceuticals, the lungs, the immune system, COVID-19. Without further ado, please enjoy. Here is Dr. Theoharis Theoharides, coming on the “GeneFood Podcast” for round number two.

Well, Dr. Theoharides, we really appreciate you coming back on the show for a second episode. As we’d discussed off the call, your wisdom and insight from the last show we did on the immune system has become more popular, in light of all this craziness with coronavirus, and people looking for ways that they can boost their own health to respond to this threat. So we’re happy to have you back on. Thanks for joining us.

Dr. Theoharides: I appreciate it very much. My pleasure.

John: And you’re coming to us from Massachusetts?

Dr. Theoharides: That is correct. I’m in Boston.

John: Yeah. Another city like my home city of New York City that’s had a tough time with this whole…

Dr. Theoharides: Yes, it did.

John: …pandemic.

Dr. Theoharides: This is the first week that they’re just inching the way, opening up in some additional services. The university’s still closed.

John: But the… Is the overall feeling one of optimism, cautious optimism?

Dr. Theoharides: Well, I have cautious optimism. I don’t know what the rest of the country does. But what worries me…we might talk about this a little later, is, I felt that we should have learned from our experiences over the last three months, and changed our habits a little bit. But as I see, a lot of people that are now out in the street, just don’t keep the habits that they should have. And I was always surprised why, in crowded places…hospitals, airplanes, why there was not a directive that if someone is sick, coughing, sneezing, they should put a mask on.

I mean, every time I travel, half the plane was sneezing and coughing, and no one could care less. So whether there was flu or COVID-19, or both, we should have been much more careful about what we do when we’re sick. And we weren’t. And I thought that because of the scare and the financial and health repercussions of what we’ve seen in the last three months, we would have learned better. But I see a lot of people out there, still not using masks. And as you know, in a number of states and countries, now we have a resurgence. So I don’t know what will make people change their habits.

I remember, years back…it was about, I don’t know, nine years ago or so, I was in Kyoto, Japan during their flu season, if you wish. And everybody was wearing a mask. And we were kind of making fun of them, “Oh, look at them.” You know, I think that we’re just smarter than that, in many ways. So I wish that for the next few months at least, we use masks as much as possible. And short of that, I think science will actually deliver to some extent, although I’m not quite sure what will eventually make the difference. I really don’t have high hopes for vaccines, but we can talk about this as we move on.

John: Yeah. It’s funny you mentioned Japan. My girlfriend’s from Tokyo, and she’s in contact… We have been quarantined together, and she’s been in contact with her mother. And as I’m sure you’re aware, they have lifted the state of emergency in Japan. Tokyo’s a city just as dense as New York, just as crowded of subways as New York. And the coronavirus has…if not gone to zero, come very close to going to zero in Tokyo. And it does seem that these interventions, mast being tops among them, make an enormous difference.

Dr. Theoharides: It does.

John: Yeah.

Dr. Theoharides: It really does. There’s also been either miscommunication or misrepresentation of fact. We’ve been talking about cleaning our hands,. You know, sure it’s a good idea. It was always a good idea. But some of anti-cold bacterial soaps or gels still don’t cover viruses, and no one really talks about this. I mean, alcohol, 75% alcohol, is probably the best for viruses. And 50% alcohol, literally rubbing alcohol, that is good. So the antibacterial soaps contain antibiotics, or certain molecules that can have antibacterial action, but it doesn’t really catch viruses.

So I think the best that we can do is just use rubbing alcohol whenever we can, basically, whether it’s in a solution or some other form.

John: One of the things that we wanted to talk with you about that was an interesting section of the last conversation we had, are about these natural compounds that can boost the immune system or regulate some of the cytokine activity. We know about the cytokine storm. I think it’s an important caveat to say, “Look…” We’ve said this on previous episodes, “If you’re drinking six beers a day, and you’re eating two bags of potato chips, and you’re not exercising, there’s no natural compound that’s likely to give you much protection.”

But let’s get into some of these nutraceutical agents that have the ability to boost the immune system. You mentioned luteolin, you mentioned quercetin, pycnogenol, vitamin D. Tell us, what are your top agents out there that you’re looking at, and why?

Dr. Theoharides: Well, let’s start by first discussing the fact that three months ago, hardly anybody was talking about cytokine storms. Everybody was talking about what the virus can do. And what the virus does is actually creates havoc in your lungs that we call SARS, severe pulmonary problems. And that’s what forces, basically, the hand of the clinicians, to use intubation for these patients, because the lungs are so badly damaged, they cannot breathe on their own. So I think of COVID-19 in two stages. One stage is that it has to get into the cells, whatever cells. And we will talk about the cells.

The second stage is what the body does in an effort to protect itself. And then, all short of that…you can call it Stage Three, if you wish, is when the body overdoes it and starts damaging itself. So starting from the back forward, we know that during SARS, there is actually release of many cytokines. We called it a cytokine storm. And so far, one cytokine, interleukin 6, has been studied a little more. And there is, actually, a drug on the market that neutralizes interleukin 6. And it has been tried in a clinical trial in New York, and I think it’s a wonderful idea that has been tried.

However, there at least 50 different cytokines, and we usually talk about maybe 5 of them. So interleukin 1 beta, which gave the name to the family, is one. Then, it’s interleukin 6, there is interleukin 33, there’s interleukin 31, there’s interleukin 4. There are drugs for some of these out on the market, for different reasons. For instance, there’s a drug that neutralizes interleukin 4 for asthma. I’m surprised why it hasn’t been tried so far. There are four drugs that neutralize interleukin 1, and we use it for psoriasis, rheumatoid arthritis. Again, I have no idea why they haven’t been tried so far. We have the evidence that these cytokines are being released.

Instead, we spend months discussing those anti-malarial drugs, chloroquine and hydroxychloroquine which, study after study after study, has been shown to have no benefit and doubles the risk of dying from a heart attack. In fact, just yesterday, one of the major studies was withdrawn from a journal, “Lancet,” one of the big journals in the world. Where it had originally indicated there might have been some benefit, it was withdrawn, because the results were not there. I’m not going to go into why it was accepted to begin with, but we wasted three months. And due to… The president went on board, probably misled himself about the benefits. And as you know, we were talking…he was talking about the benefits.

So what do we do, other than blocking or neutralizing the cytokines after they have been released? The drugs that I mentioned would be helpful…and I wish that there will be studies forthcoming soon, but after they have been released. Can we block the release of the molecules to begin with? And that’s where some of the nutraceuticals come in. We have known for many years that certain natural flavonoids can actually inhibit release of such cytokines for both macrophages and mast cells, the cells that primarily release these cytokines.

The difficulty is that many of these studies have not been done properly. What do I mean by that? They might have used an extract, but not the pure material. They might have used a pure material, but only in animals. They might have used a pure material, but either with or without food in patients that do have problems or in normal volunteers. So it’s very difficult to know the exact amount that is necessary to block the release, and how to best give it. Having said that, from all the studies, it seems that quercetin and luteolin have been the most potent in most of the studies out there. Now, what is the difference between the two? Very little.

Just think of three rings tied together. We call those phenolic rings. And then, on each one of those rings, there might be an attachment of something that looks like water. We call it a hydroxyl group. So water is two hydrogens and an oxygen, and a hydroxyl group is one oxygen with one hydrogen, because one hydrogen has to go away to allow the molecule to bind to the rings. So the more hydroxyl groups we have, the more phenolic a compound is. What does that mean? We used to think that the more phenolic a compound, the better it would be. And it turns out that that’s not the case.

So we separate the actions in two. One is antioxidants. And we know that we call oxides and radicals are bad. So the more phenolic, the more antioxidant a compound is. But that doesn’t mean that it is more anti-inflammatory, because we’ve published a number of papers, four of them in the proceedings of the National Academy of Sciences, showing that tetramethoxyluteolin that has no phenolic groups, is more anti-inflammatory. So basically, we’re trying to combine molecules that have a lot of antioxidant and a lot of anti-inflammatory activity. And therefore, we have to get a ratio of the two.

So we’re a proponent of mixing quercetin and luteolin for that reason. Quercetin’s a little more antioxidant, luteolin’s a little more anti-inflammatory. And in fact, there are studies that if you combine the two, you get better benefit, overall. And what is the problem? The problem is that all of these flavonoids are very poorly absorbed from the intestine in a powder form, less than five percent. And in fact, there are studies shown that if you approximate what we use in the laboratory… And the laboratory can… We can block cytokine release, 100%. But we need a certain amount, which of course, the cultured cells see right there and then.

There’s no absorption problem there. The mast cells or the macrophages will just be looking at whatever the suspension or the solution needs. But if you were to take that amount and try to now approximate a human body… And when we approximate the human body, we usually say a body’s about 100 liters, roughly, about 100 kilograms. And that you have to have your flavonoids 100% distributed throughout the body, but that’s impossible, because only about 5% to 10% is absorbed. So there must be ways to increase the absorption.

Some ways are pharmaceutical, and we don’t have access to them. Some are a little simpler. So if you take these flavonoids, whether it’s quercetin or luteolin or the combination, you put them up in oil, and you basically shake up the oil…you give, basically, energy to the oil. You can do that by sonicating with a probe sonicator, or by mixing it up very quickly, or shaking it, some of the oil becomes little spheres, because this is the least energy-acquiring configuration, three-dimensional. And in the process of creating those little spheres, they trap inside, the powder.

Now, some of the spheres are a little bigger, some are smaller. We call those liposomes or phospholipid vesicles, in that dietary supplements, there’s no way to control the size of these vesicles. So basically, when you shake up the oil, you get some bigger, some smaller. And eventually, we found this in animals…that was about 10 years ago, that we can increase the absorption from about 5% to about 30%, if we use olive pomace oil. Interestingly enough, the French, in various cosmetics, they use it heavily now. They call it “olive fruit extract.”

It sounds better to say “fruit,” and it sounds better to say “extract.” The bottom line is, it’s exactly the same material, whatever you call it. It’s just marketing. Now, going back to your original question, there are such supplements mixed with olive pomace oil to increase the absorption. And the ratios are different, depending on the makeup of the people. Not all the people are the same. That, we created before COVID-19, knowing that we can inhibit the release of the cytokines. So when COVID-19 came around, we were aware of the fact that there will be cytokine storms. Therefore, giving individuals such…either single or a combination of flavonoids could only help reduce the release of the cytokines.

While we were actually doing this, three wonderful papers were published within the last two months. And then, I discovered a paper that was just published, also, about five years ago that all converged to the same thing, which is the following. COVID-19… By the way, COVID-19 as the disease, it’s not the virus. The virus is SARS-CoV-2, because eight years ago, we had SARS-CoV-1. And about 19 years ago, we had SARS by itself back then. So COVID-19 is the…all the effects that the virus basically ends up creating in our body.

We thought it was only the lungs, then we’ve heard about clotting problems, then we heard about meningitis, etc. So I think the conglomerate of the symptoms is COVID-19. SARS is literally what happens in COVID-19, primarily in the lungs. So a number of colleagues identified that the corona of the virus, has spiked. And part of the spike protein…so it’s a unique protein when it’s spiked, has the ability to bind to the surface of certain cells, especially in the lungs. Where does it bind? Other colleagues have identified that there is an enzyme sticking out of the surface of the target cells, and that enzyme acts as the receptor.

That enzyme has been identified as Converting…Angiotensin-Converting Enzyme 2, a well-known enzyme. We’ve known it because of hypertension and other problems. Now, why the virus developed in such a way that it binds to that enzyme, no one knows to date. But we know that it binds. So about five years ago, a paper was published that I wasn’t aware of until I started looking into this area, where they took, actually, cells. They tried to infect them with the old SARS Type 1. So SARS-CoV-1, not the new virus. And they showed that luteolin blocked the binding. I had missed it altogether.

And no one, I guess, made much of it, because it went unnoticed for about five years. But as I was looking at the literature, three other laboratories used simulations by taking the enzyme that act as the receptor… And every enzyme has what we call an active site. That’s where the job is done. So the active site of the enzyme, if you can imagine it sticking out of the cell, is where, now, COVID…my right hand, fits in there. And once it fits in there, then it could get into the cell and infects them. So what they did is, on a computer simulation, they created this active site called the Converting Enzyme Type 2.

And they’ve tried to find out what molecules are out there that can fit into that same group, and therefore, block the binding of the spike protein. And they used… The fastest computer in the world is called Summit, S-U-M-M-I-T. And they screened 1.3 billion…not million, billion molecules. And they found that about 20 molecules could actually block the binding of COVID-19, if you wish, or the virus for COVID-19. Some were all drugs, and two were natural molecules. And I was absolutely elated. One was luteolin, and one that was 99% similar to luteolin…even more similar than what quercetin is similar to luteolin, called eriodyctiol.

The only difference with luteolin and eriodyctiol is that one of the rings is not a benzene ring, for the chemists out there. But it’s still the same hydroxyl group, same everything, except that the center ring is not a benzene ring, as we call it.

John: Now, could I just ask you a question about that?

Dr. Theoharides: Yes.

John: So in nutrition circles, there’s a lot of debate about soy and estrogens versus phytoestrogens. Is the binding of the natural compound, like luteolin, to the ACE-2 receptor kind of the same thing as you get, the plant estrogens, the phytoestrogens binding to the estrogen receptor, which blocks the docking of the actual hormonal estrogen?

Dr. Theoharides: Your… Yes. Your knowledge is correct, except that in this case, the binding has nothing to do with estrogen receptors. But yes, you’re right. Right.

John: Right. Yeah, the analogy is there. Right, okay.

Dr. Theoharides: Which brings me, basically, to two more… I know I gave you an earful, but I just want to kind of give you the overall picture. So before we talk about some of the pluses and minuses of the flavonoids in general, I literally think that by using the right combination of quercetin and luteolin in a formulation that allows better absorption, it’s basically catching two birds with one stone. Because you can… Giving it prophylactically, you can at least reduce, if not block the binding of the virus to the cells. And that if the virus is there and starts creating release of cytokines, you will block the cytokine release. And there’s literally no downside.

John: So you’re saying that these natural compounds, quercetin, luteolin, they could stop the infection process, essentially?

Dr. Theoharides: That is correct. But it all depends how much you get into the blood. Because if you don’t get enough, obviously, you’re not going to make a difference.

John: And were these studies…? You said they used a computer simulation. Were these other studies…? Were these in vitro studies, were these animal studies? What do these studies look like, that looked at these compounds?

Dr. Theoharides: So the three large studies…now they’ve been referred to, actually, more and more in various good journals, were done by simulation. So there was no real cells, okay?

John: I gotcha.

Dr. Theoharides: We did one study just before the labs were shut down. And I sent you, actually, a little publication that not only has been, now, on [inaudible 00:25:14] for two weeks. But I was notified that one of our graphics will be used for the cover of the journal. The journal is called “BioFactors,” and the May issue of “BioFactors,” our paper was published. The problem with the flavonoids, in addition to being very difficult to absorb, they’re very difficult to put in solution, as well. Basically, the absorption problem is the same. If you can’t put something in solution, you won’t be able to absorb it very much, as well.

So the good formulations have to overcome both solubility…what are you putting in, so that it’s not a powder, and eventually, the absorption. Now, when colleagues hear, “Oh, my God. We’re not going to absorb a lot,” what do they do? Well, we’re going to give them grams of material. It’s the obvious…and I’m sorry to say, silly approach, because that’s not the way to do it. And the reason being…and I’m being asked this all the time. If I were to give, as some of my colleagues do, five grams a day of quercetin, or luteolin for that matter, I’m going to shut down all the gut enzymes and all of the gut bio-flora. And their publications are there, that that’s what happens.

So you literally destroy the gut flora, if you were to give that much. So by giving a lot, you hope, let’s say, 10% is absorbed. You give one gram, that’s 1,000 milligrams. Hopefully, you will absorb 10, so you’ll absorb 100 milligrams. But if you were to give five grams, all of that is going to be, actually, in the gut, and your gut will be a mess.

John: Why? And why does taking that much quercetin damage the gut?

Dr. Theoharides: Because it will stay in the gut, it doesn’t get absorbed. So put it differently. Let’s say I give you 100 milligrams, and you absorb 10 milligrams, let’s say, 90 milligrams left in the gut. Well, it’s not much to do anything, really, so I’m not worried. But if we were to give, let’s say, 10 grams, and you only absorb 1 gram. That means nine grams are going to be there, sitting in the gut and inhibiting everything in your gut. That’s why. The best way would be to use a different formulation.

And believe me, I approached five different companies, some small, some large, because after all, SARS is in the lungs. And I said, “Wouldn’t it be wonderful if we were to take luteolin, or quercetin and luteolin, and put it into, basically, something that I can spray in the mouth?” I mean, we have such sprays for asthma galore. Not with flavonoids, but with other drugs. So why couldn’t we just do an inhaler with these molecules? In which case, we deliver most of what we want directly to the lungs, no problem with absorption whatsoever. And we will get it right where the action is as well.

And no one seems to be interested, because there are no blasted patents, okay? And I even wrote literally… I swear, I wrote to the president of the United States through the White House portal. That’s the only way. It’s been about two months, no one has answered, even an acknowledgement. And you know, with all my credentials… I’m sure they get a lot of emails. But on the other hand, I’ve seen so many other people showing up on various forums with less useful information. So how are those picked versus some of us who might have more of something?

Why did I do that? Number one, because I wanted to tell the president… And I wrote to Dr. Fauci, he never replied, that there is material here that could help a lot of people, no side effects. And companies are not interested because there’s no patents. But the president of the United States, any president, has the authority with his signature, to change the field. For instance, companies that make vaccines, they don’t make a lot of money. In other words, let’s say that you know, at least if something has been discussed, why didn’t we have vaccines when we had SARS-COVID-1, 10 years ago? Why didn’t we create vaccines then?

Well, because not too many people died. And the companies said, “Well, how are we going to make money out of this? No one’s going to be taking it, because no one is really in danger.” Now, if any president…whether it was Obama or Trump or anybody, really had seen forward…if they had a little more vision, they would have said, “Well, let’s take some company that are not likely to make money. But let’s give them money to make the vaccines and have them ready.” So we were literally caught with our pants down. We could have had vaccines, because it turns out that COVID-1 is about 95% similar to COVID-2. Not identical, but we would have had a lot of information.

So what I’m saying is, the president of the United States can basically say, “I will give any company that takes this and makes,” let’s say, “an inhaler 10 years exclusivity. It doesn’t matter the patent, no one will be able to copy it.” He can do it. And therefore, companies would have an incentive to do it, even though they might not make a lot of money. This is what I call vision. And not only about COVID-1, about other things as well. We are always dependent on whether a company has or doesn’t have a patent, and usually, a strong patent. But this doesn’t have to be that way.

So I think… And I’m saying this because you probably know it. But I’d spent, actually, a good portion of time at the Kennedy School of Government at Harvard, and at the Fletcher School of Diplomacy at Taft, basically studying and discussing and writing about biomedical policy. It shouldn’t be just that NIH gives money if you write a good idea, because those good ideas have to be competitive, which builds the concept or the framework of what other colleagues do. It’s very difficult to get something funded if it’s off the beaten path. And it’s impossible to get it funded if it is a natural molecule.

For instance, the reason the vision of NIH… Which is called the Institute of Complementary and Alternative Medicine, okay? I wrote to them, and I told them what we’d be discussing. They were polite, they answered back. And the answer was…and I have it in writing in an email, “It is very timely, but we’re not interested.” So there you go.

John: Yeah. And…

[Crosstalk 00:31:47]

Dr. Theoharides: [Inaudible 00:31:47].

John: It’s that difficult conversation that you have in all these medical and nutrition conversations, of what comes first, the chicken or the egg? Do you first have the nutrition and nutraceutical research, or…to develop the science? Or, do you get the funding and the people that are anti-nutraceuticals say, “Well, there’s no science on that?” And then, the people that think that there’s more premise for the natural compounds say, “Well, there’s no science because there’s no profit incentive,” and on and on the circle goes?

Dr. Theoharides: You’re right, to a large extent. But without necessarily patting myself on the shoulder, we have five publications with luteolin and methoxyluteolin in the “Proceedings of the National Academy of Sciences,” one of the best journals in the world. You know, been peer-reviewed galore. So what more science does one want? Not addressing this to you, just in general.

John: No, of course. Yeah, no. I understand.

Dr. Theoharides: But in something like this, I dare say, you really need someone… And I’m only throwing names, whether it’s [inaudible 00:32:47], whether it’s about Google, whether it’s…anybody, Facebook. Some people that clearly have a lot of money…in which case, a little bit of money is not going to bend them, who think, basically, outside the box, who maybe are social or health-minded and say, “Wait a minute. Here’s a good idea. How much money do you need?”

Not me personally, or a company. “Show what could be done.” If I can make an inhaler and I can infect mice… Not I. I don’t have the laboratory security for that, but other people do. And then, we can actually show that it blocks COVID-19, and SARS goes down. These are easy experiments for laboratories, whether within the NIH or other universities, that have the security to do the COVID-19 studies. So we’re not talking about anything [inaudible 00:33:37], and we’re talking about 100,000-plus people that died. So why are we not moving faster?

John: There’s been a lot of commentators that have been sounding the alarm on that. I mean, one of the big ones…and maybe you would be helpful to give a little one-on-one on a couple of these natural compounds. But one of the big ones that people are talking about is, “Why aren’t you basically telling the public…?” We said masks. “Why aren’t you telling the public to take vitamin D?” And so, I don’t know…

Dr. Theoharides: Okay. Let’s talk about [inaudible 00:34:04]…

[Crosstalk 00:34:04]

John: So let’s do vitamin D, quercetin, luteolin, one-on-ones of each of these different natural… I think, some very top-level stuff people would benefit from.

Dr. Theoharides: Okay. So since we spent so much time talking about the flavonoids, luteolin in any liposomal form that increases absorption is high on my list, okay?

John: Okay.

Dr. Theoharides: Quercetin, but no more than about a gram and a half a day, okay? If someone wants to use quercetin, as long as they don’t have phenol intolerance…because more phenolic than luteolin. It’s a little less anti-inflammatory, so it’d be quercetin. But it’s got to be, again, liposomal of some sort. Most everything, except for one, out there is all powder forms. So you’re just not going to absorb it, it’s going to come out in your stool. Then, the combination of the two in a liposomal form would be the best, in my mind. So that takes care of the flavonoids.

Now, there are other flavonoids that we hear about many times, but they have additional problems. For instance, pycnogenol is a flavonoid found in grape seeds, but it’s very phenolic. It’s got 15 phenolic groups, quercetin has five, luteolin has four. Curcumin is flavonoid, but it’s very phenolic. And a lot of people with allergies or allergic-like symptoms don’t do well with curcumin at all, if they don’t deal with spices, because they…it acts like histamine. And it activates all that pathway.

So then, vitamin D3. First of all, the way we manage our vitamin D3 is not correct. Vitamin D3 must have two hydroxyl groups. And when we ask for it to be measured, I usually write in parenthesis, “One, 25-OH,” for hydroxyl group. Now, the fallacy is that we are out in the sun, we get a lot of vitamin D. That’s not true. Our skin has three vitamin D’s, so the sun will change it to vitamin D. But then, it has to go through the kidneys to add a hydroxyl group, then to the liver to add another hydroxyl group. And that’s vitamin D3, the active form.

In about 40% of the people, even in countries like Sweden, Cyprus, Greece, have actually… And I mentioned those countries, because some countries have a lot of sunlight, like Greece and Cyprus. In Sweden, obviously, they don’t get enough. And yet, we have about 40% vitamin D3 deficiency. So it’s very important to be giving vitamin D3 in general, but there’ve been a number of studies that vitamin D3 is both anti-inflammatory and anti-allergic. The journal “Clinical Therapeutics,” two years ago, had its whole May issue dedicated to the effect of vitamin D3, which is actually anti-allergic and anti-inflammatory.

So I always recommend at least 2,000 units of vitamin D3 a day, in whatever form you can get it: to spray in the mouth, into your Gummy Bears, into capsules, whatever.

John: What do you think about pairing vitamin D3 with K2? That’s a common formula.

Dr. Theoharides: Okay. I have no objection to combining it. In all honesty, I have no idea what K2 does. We’re more likely to suggest K2 and vitamin D3 for individuals that have neuro-psychiatric problems, because there’ve been some reports that it might help. But even those reports were not actually well-documented. But I have no objection from what I know, at least. I don’t think there’s any reason to give, as some colleagues do, 50,000 [inaudible 00:37:52] units of vitamin D3. It’s way too much, you’re going to get rid of it very quickly, and it does have its own side effects, if you reach that level.

Now, after that, there are a number of molecules that have, actually, anti-viral activity. But it depends on its purity. For instance, we know about St. John’s Wort as having anti-depressant properties. At least, that is being publicized quite a bit. It turns out, there are about 10 publications that it also has antiviral properties. But it depends how pure it is, and how much you get into the body. Same thing with berberine sulfate. It’s got antiviral properties, but it depends how much you take. And you can’t just, say, go and take it. For instance, berberine sulfate is very bitter. So if you give a lot, depending the formulation, you might not be able to tolerate it.

And there are a number of other herbs, if we go down the list, that do that. Sulphorathane, which is found in broccoli…and now, there are a lot of supplements out there, also has been reported to have antiviral properties. And again, it all depends. If you just get a broccoli extract, that’s not going to have… That’s less than one-thousandth of the sulphorathane that you need, to have antiviral properties.

This is why, at the end, we decided to create a new supplement. So we already trademarked and bought the domain “Viral Proteck.” Keeping with “Neural Proteck,” “Viral Proteck,” with a “K” at the end. It will be available around September through Amazon, and it will contain five ingredients. We’ll have luteolin, we’ll have quercetin, we’ll have eriodyctiol, that I mentioned earlier. It will have sulphorathane, and it will have another molecule that for the time, I’d like to keep it quiet.

John: Interesting. For the sulphorathane, Dr. Theoharides, do you use glucoraphanin? My understanding was, glucoraphanin…which is, I guess, a precursor to sulphorathane, is more stable in supplement form. Do you…? What’s your take on that?

Dr. Theoharides: Okay, that is correct. If it’s not one that I would have… Because sulphorathane, if you were to buy it bulk, it comes as 5% purity or 10% purity. If you were to buy this 100% purity, it’s extremely expensive. Same thing… Eriodyctiol is found quite a bit in lemons, just to give you an idea. But you know, how many lemons can you squeeze and drink? It’s sour, as well. So if you were to get, let’s say, 10% purity eriodyctiol…I’m just giving you an idea, it’s about $500 per kilogram. You get it 100%, it’s $30,000 per kilogram. But obviously, the purer it is, the more likely it’s going to have the benefits that we know from studies done with cells, rather than whole individuals.

John: Eriodyctiol, I have not… It could be that I haven’t heard of that compound. Is that…? That’s not an adaptogenic herb, is it, in lemons? Tell us about that. That was not on my radar at all, as a natural compound.

Dr. Theoharides: Well, it wasn’t on mine, until I actually saw all those simulation studies, where they called it at the top of the list to block, basically, COVID-19. So…

John: Would you get that from lemon balm? If you took lemon balm supplements, would you get that?

Dr. Theoharides: Well, it’s… All of these flavonoids are very rich on the pulp and the skin of the fruit. Same thing with citrus fruits: you know, oranges, grapefruit, etc. Not in the juice, etc. So you literally have to chew lemon peels to get anything out of it. There is another molecule that is also quite popular, not as well-studied, in lemon called hesperidin. It’s another flavonoid, it’s very similar to quercetin, except that those hydroxyl groups are in different positions. Same idea, though. Also quite effective. So…

John: What about zinc? What about zinc?

Dr. Theoharides: I have no evidence that zinc does anything at all, to be honest. Zinc is… I can theorize from biochemistry, zinc is very important for a number of enzymes to do what they do. If you have a zinc deficiency, you’re going to have a lot of problems. So by giving zinc, if there is any deficiency, you might be able to help some enzymes along. But I don’t know of any studies that zinc has direct activity against viruses. It might be helping certain enzymes that can chew up the virus, but I’m not that knowledgeable in that area, to be honest.

John: And what do you think of colloidal silver?

Dr. Theoharides: Well, I don’t like silver at all. We did some studies with colloidal silver about 15 years ago for a disease called interstitial cystitis. And that’s also called painful bladder syndrome. Many people can have that, if they have chronic fatigue, fibromyalgia, mastocytosis. About 60% of the people have these comorbidities. And maybe because the mast cells are involved, we can maybe talk a little bit about this later.

But we had created a model that other people use, too, by putting certain things into the bladders of rats, creating inflammation in the bladder. And we would have, basically, the rats… This was an approved study, don’t get me wrong, by the appropriate committee at the university. But we would have them in what we’d call biologic cages. So when they would urinate, we will collect the urine, and we’ll… The urine will drop from the cage, not in the caging, into a container. And the container was on dry ice and will freeze the urine, so we will be able to analyze it, because you don’t collect the urine 24/7.

And there, we’d try to inhibit the bladder inflammation by instilling certain substances. And we use silver, basically, colloidal silver. It did have an anti-inflammatory effect, but it was very difficult to handle, and it was absorbed quite a bit. And I got worried about the absorption of the silver, and what that would do.

John: But it bio-accumulates, right? I mean, you have, in… The English royalty who drank and ate from silver would… They would develop, essentially, silver toxicity over time, correct? They would…?

Dr. Theoharides: Of course. Of course.

John: Yeah, yeah. Yeah.

Dr. Theoharides: Yeah. And there were a lot of individuals who would react, even, to silver jewelry. And they get a topical reaction, basically, contact sensitivity. Copper is the worst, but even silver can do it in some individuals. But I don’t have… I really don’t have enough experience with metals, let’s put it this way. However, I want to go back to what you said earlier. And this is something that is used in one form or another, in many labels, forms, etc. Some labels say “immune boosting,” some say “neural regulation,” etc.

I’m not sure that any of those terms are correct, because in certain conditions, we want to downplay the immune systems, in certain conditions, we want to really increase the immune system. There’s no such thing as something the encompasses everything about the immune system. And let me make the following point by using COVID-19. Colleagues have published very good papers that the immediate protective reaction of the body against COVID-19 is…against other viruses as well is, number one, to make antibodies that try to neutralize whatever they can neutralize.

In this case, they might neutralize the spike protein, so that the spike protein cannot actually attach to the receptor. Or the antibodies may cover the virus, because the macrophages that eventually…or the T-cells that are the cellular immunity need to recognize something when it is presented to them in a particular form. And many times, it has to be bound to an antibody, in order for those cells to recognize it efficiently. So the antibodies will be created fairly quickly. They might not be protected, they might only allow the rest of the body to recognize the virus.

And then, the T-cells…”T” because we thought they all come through the thymus, which is spelled with a “T,” that’s why “T-cells,” are the ones that basically deal with anything that is intracellular. And the viruses go inside the cells. So we know that we need antibodies, and we need T-cells. We do not need cytokines. Two studies have been published, one from England, one from China, in patients with COVID-19 that survived. And they showed that they had antibodies, the T-cells were activated, but there were no cytokines in their blood to talk about.

So therefore, the cytokines, unlike other diseases, don’t seem to play a major role in COVID-19. And instead, they’re the destructive elements of the body, where the body basically, at some point…especially in the lungs, when the cells get infected, says, “I’ve lost it. The T-cells are not helping, the antibodies aren’t helping. So I’m just going to throw, basically, the waterfront at the virus.” And that’s what basically happens, and it’s self-destructive. That’s why it’s important to know what part of the immune system is important.

Because if we were to say we want to boost the immune system so that it makes more cytokines, then we’re basically not protecting ourselves, and we’re likely to actually destroy ourselves even more. If, however, we were to say we will give something that will activate the T-cells so they recognize the virus, then yes, I will say we need that. But we cannot say that with just one slogan. And it’s very confusing to, I guess, pretty much everybody, but especially to the lay public that thinks that the immune system is necessarily good.

Just think for a second. Rheumatoid arthritis is the immune system destroying ourselves. Lupus erythematosus… And we heard this in many children, that it creates a lupus-like reaction. It’s also autoimmune, the immune system attacks the body. Psoriasis is the immune system attacking. Multiple sclerosis is the immune system attacking. Asthma is the new system attacking, inflammatory bowel disease. So in many of the major diseases, we do not want to increase the immune system at all. Because from my end, that would worsen the problems.

John: It’s such a great point. And it is confusing out there, because as I have… And I’m following the COVID-19 conversation, and even commentators that I trust and respect, you’re hearing different things. Some people will say, “Oh, well, zinc can… Zinc gluconate is terrible, because it does this with COVID-19. And actually, you don’t want to take vitamin D3 supplements, because it can do this to the ACE-2 receptor,” and on and on and on. And so, it’s really difficult to find accurate information, which is why we wanted to have you on. And then…

Dr. Theoharides: Thank you. One of the things that I have not seen, that you might be in a position to do it… And I’ll be very happy to help along, not that necessarily, you have the right answers. But I haven’t seen any site from any patient group or any company, for that matter, including Algonot that makes the supplements…and I’m trying to help them do that, a good Q&A online about questions like the ones we’ve been talking about, questions that patients come up with. So that someone can answer them…

Again, without necessarily saying one is the authority, at least put some answers out there, so that someone can visit, let’s say, your side. And you can put the Q&A with whatever, and they can just go visit. And they might give you credibility over and beyond what you already have, by providing a service that is just not out there. What we discussed today, I’ve said to other colleagues, I’ve said to other patients… I get questions all the time from patients and colleagues. I got a question today, for instance, from a physician who basically said, “If someone is taking,” you know, good question, “chemotherapeutic agents, can they take these supplements,” for instance?

And my answer is absolutely, “Yes.” It has nothing to do with the chemotherapy, unless someone is taking hormonal therapy for breast cancer, which is positive for estrogen receptors. In which case, you don’t want to give them phytoestrogens, you know?

John: Yeah. I…

Dr. Theoharides: You know? But… Yeah.

John: The Institute for Functional Medicine did put out kind of a…what’s meant to be a sort of comprehensive guide to herbs and nutraceuticals and the immune system and COVID-19, which is fairly well-done. But I agree, they’re… I mean, I… A lot of people, even Joe Rogan on his podcast, has called and said, “I wish that the…” and said…echoed exactly what you said, which is, “I wish the government would be a little more proactive in telling people in its messaging that, “Look, there are ways…”

Again, it’s not going to save you from a terribly unhealthy lifestyle, or eating two pints of ice cream a day. It’s not a cure-all pill. But there are ways that you can, in a sophisticated way, enhance your innate response to these things.

Dr. Theoharides: Look, I wish both the government and the NIH had done that, instead of talking or keeping silent about hydroxychloroquine and other such drugs. They did so much damage and so much disinformation, while they had every chance in the world to help people along. And with that, I’d like to make a comment about vaccines. I started talking about it earlier.

John: Please do.

Dr. Theoharides: Yeah. I really take issue with Dr. Fauci and others, who keep on saying, “Oh, we’re likely to have a vaccine,” whether it’s 6 months or 12 months or whatever, “and everything will be fine. I will be the first to cheer, if we have a vaccine that is help…beneficial or effective. However, we’ve known about flu for hundreds of years. And if you were to just look at the site, CVC or NIH, the effectiveness of the flu vaccines in the United States over the last three years varied between 10% and 40%. Ten percent. So what are we talking about here? Literally, that is not an effective vaccine, period.

Number two, by telling people, “Oh, we’ll have a vaccine,” we basically keep them from being proactive of putting masks on, or whatever. Because if we knew the vaccine is truly 100% effective, sure, I will relax, too. But when I know that a vaccine is only 10% effective, I cannot just not take other precautions. So we’re giving, basically, disinformation at two levels. One, that the vaccine will be effective, which is not true, because it hasn’t been true for the flu. Second, that it’s not enough to have an effective vaccine, no matter what.

Now, I come to COVID vaccine by quoting what is out there. Oxford Pharmaceuticals, which is one of the ones that is most likely to come up with a vaccine sooner than anybody else, the chief scientist came out and he said, “Maybe 50% effective.” That’s what they said, number one. Number two… This is being discussed heavily. The government, through different means, gave two contracts for vaccines. One was $1 billion, and the other was half a billion dollars. But even scientists that know about viruses…not myself, have said that neither one of those companies had ever created a vaccine. No track record at all.

So why were they chosen? On what basis? Why do we expect that those will do any better than the [inaudible 00:54:33] or the Regeneron, or companies that have been putting useful drugs for years on the market? It’s beyond me. No one understands it. Now, having said that, there are three things that we don’t know. And again, those are not being discussed. Number one, let’s say we make antibodies. Are they protective, and for how long, for ourselves? Number two, are they neutralizing the virus? Or are they basically keeping it from infecting us, but the virus is there? And I’ll give you an example in a second.

Which means that I may be protected, but I might still harbor the virus and infect you. And finally, are those antibodies…? Where we transfer them, because we’ve heard about transferring antibodies and helping people, especially when they were intubated. How long are they going to stay in the body and help? Usually, they’re gone by a week. So if we were to transfer antibodies to someone, because they’re foreign antibodies, they’re basically gone. So we might be able to…and don’t get me wrong. Say someone was intubated at the deathbed, but that might not be the way to treat everybody else for months.

Now, Regeneron, a wonderful company, as far as I’m concerned, had created antibodies in the laboratory when Ebola was going crazy. And they helped a lot of people, because they can take the organism, and they can identify what we call epitopes to what part of the organism an antibody can be made. And they made antibodies, and they can inject those antibodies. And those stay for quite a long time. It’s not a vaccine, okay? But for those who are infected, those might be able to protect them from going into SARS, etc.

So those are good ideas. And I think those types of antibodies, whether it’s a Regeneron or someone else…and I have no stock, I wish I did, in Regeneron, will be helpful within, I think, the next nine months at best. And so, I have…

John: Interesting.

Dr. Theoharides: Yeah. I have very high hopes for those antibodies, who those are infected. A final problem… And I know I’m giving you an earful. But we’ve heard all along that the tests for whether you’re exposed to the virus, let alone whether you have antibodies, have a lot of false negatives and false positives. Some colleagues say that they’re as high as 30%. And I’ll give you an example of a friend who is actually a physician, who flew from London into Cyprus. He was tested, as they do…and I’m glad they do, something they would not do, as they had here, everywhere.

So he was tested for COVID-19 at the airport. He was negative. And nevertheless, as Cyprus does…and Greece does the same thing, he was put in quarantine for 14 days. Now, at the end of 14 days…I heard this yesterday, he was re-tested. And now, he was positive. Well, how could that be? We usually say that even if someone is positive, 14 days in quarantine will clear it. And here, we see the exact opposite. And I’ve heard this four times over the last week from various countries. So either the first test was a false negative, or the second test was a false positive. Now, what do we do now?

And we will have a lot of those individuals. That’s why it’s so important, this test, to be, like, 90% specific and 90% sensitive. So 90% sensitive they will pick it up, it will be true positives, and specific that we’re not going to have false negatives, basically. And we’re not there yet.

John: Yeah. I was… Speaking of this whole virus-antibody-vaccine conversation, we’ve had on guests that have echoed your sentiment, which is that it’s… You know, be cautiously optimistic about the potential for sort of a widespread vaccine. But I was interested to study some of the history of this, and to see that the 1969 avian flu, which killed 100,000 people had two waves, is still circulating today. I’ve found the research kind of sobering, but also hopeful at the same time, because I said, “Okay. Well, that killed about the same number of people that this seemed to have killed.” It’s still circulating, but for whatever reason, it became less virulent over time. Do you see something like that possibly emerging with COVID?

Dr. Theoharides: It will. First of all, the virus will go through whatever iterations, and I don’t think it keeps on going. Viruses just…at some point, just adapt to the humans. I mean, we’ve had… These are called retroviruses, and it’s an RNA virus. We’ve had RNA viruses incorporated into our own genomes for millions of years. Come to think about it, I actually wrote a paper some years ago, that if you were to count… Not about viruses, just the bacteria we have on our skin, in our gut, in our lungs, in our mouth. And if you take into consideration that the mitochondria that make energy in our cells were bacteria that became symbiotic with our cells billions of years ago, the bacteria outnumber our cells at least 10 to 1.

So literally, which is bacteria that…getting a kick out of us, if you wish. There was a wonderful scientist author, Lewis Thomas. He was dean of Yale Medical School, and later became president of the Sloan-Kettering Concert Center. He passed away some years back. He used to write in the “New England Journal of Medicine” little editorials called “The Notes of a Biology Watcher,” and then, he made them little books. If you ever look him up, you will enjoy them. Each one takes, like, half an hour to read, but they’re wonderful. So one was called “Listening to Mahler’s Eight Symphony.”

And the take was, if you think you’re enjoying listening to Mahler’s eighth symphony, think twice. It’s a few billion bacteria that really are enjoying it, and you think you are. Obviously, he’s stretching it. But at the end of the day, if you [inaudible 01:00:54] viruses that are incorporated into our genome, we’re really, I mean, just literally an incredible machine, just harvesting these organisms and carrying them along.

John: But over time, as people have been exposed and… Is it that people have been exposed, and so, therefore, we develop immunity? Or is it just that the virus has less of an appetite for death? I mean, how…? So what is…? How do you make this distinction?

Dr. Theoharides: I think, both. First of all, as you know, in order to study any virus, we have to grow it into cells. For instance, HIV was grown into kidney cells. You cannot study it, otherwise. You cannot make antibodies, you will not…you cannot make vaccines. And that is an important point, because as you know, COVID-19 presumably came from bats, but it cannot jump species. We know that. So either there was an intermediate host, or it was adapted to humans.

Now, most likely, some laboratory was studying the virus…because we have to study it, I’m not saying it was done on purpose, and someone got infected. Why am I saying this? Because when we grow viruses… And I used to used viruses for other reasons, in order to blend cells and study what happens when you blend different cells together. But when you study a virus, you put the virus, let’s say, on cells, on human… Let’s say you put them on human mast cells. What is likely to happen? Either one of three things.

Either nothing will happen, meaning the cells will not get infected or be activated at all. Or the virus will infect them, but it will just burst the cells, and it will not basically be able to live inside the cell and reproduce. And that’s what happens with bad viruses. We try to culture them with cells, and they just die, and we don’t have a way of keeping them alive to study them. Or it will infect the cells, and it will adapt itself inside the cells. Now, is this a mutation? Is this some other type of adaptation? I don’t really know.

And eventually, if it does that, it’s likely to stimulate the cells to release cytokines and other things. But many of the cells, when they’re exposed to viruses, just die. And if the cells die, the virus will die, because it will not have a host. So since… Let’s go back to the flu. I mean, the virus has been with us, and it keeps on mutating. That’s why every vaccine is not as effective as the previous vaccine, because they’re now different species, different types. So I think both happens. The body creates some kind of immunity. We don’t kill the virus.

As you know, herpes virus one, every time we get upset, we create little ulcers in our mouth. That basically, Herpes Type 1 that is hibernating into the trigeminal nerve that sends three branches, one to the forehead, one to the chin, and one to the gums inside. And the virus comes out and creates a little ulcer, and then it disappears. It’s with us. It’s hibernating inside nerves. We’re not really getting rid of it. So I have the feeling that the same will happen with COVID-19, and probably other viruses. It will find a way to hibernate somewhere, and it will just keep there. And it will probably not do anything, just not multiply, until something happens.

Now, in Herpes 1, usually, it is the stress. Why stress? We can go into it. I have my own theories as to why stress, but so be it. Now, with COVID-19, who knows? Maybe difference in temperature, maybe another disease, maybe something will make it. But I don’t think the viruses disappear.

John: It doesn’t disappear, but… So, I guess, just to put a finishing touch on this line of thinking. So you see vaccine much more speculative than maybe some are reporting. But are you…? In your own way of creating your framework for this, in terms of the future, to the extent we can predict it, you see what, a second wave, and then probably a decline?

Dr. Theoharides: But I would be inclined to say yes. And if you want a final touch for the vaccines, there was a gentleman on, I think, CNN the other day…maybe another channel, I don’t remember, who is an expert…a PhD expert on bioterrorism, working with, basically, the government, Homeland Security. And he himself said that even for bioterrorism… We call it bioterrorism when someone is going to use a biological for terrorism. And he used the term “natural terrorism.” When things happen in nature, what do we call that?

And he himself said that even the Office of Homeland Security should have been more prepared for such pandemics. Which, why should it be only bioterrorism? It can be just a pandemic, as it happened for no reason at all. And yet, they were not working towards that angle. But then, he went on and said something that absolutely floored me, but I was not that surprised at the end. There was a questionnaire, not necessarily by Homeland Security, but he referred to it. I forgot who did it. A questionnaire was circulated to X number of Americans.

And the question was, “Knowing what we know about vaccines vis-à-vis the flu, and knowing what COVID-19 does, if I were to give you…I have a vaccine for COVID-19, would you take it?” Fifty-nine percent of the people said no. So even if we had a potentially effective vaccine, people would be skeptical, because they would be worried. So we have that additional problem.

John: Do you think that’s a function of people being skeptical in general about vaccines? Or do you think that’s a function of the fact that some of this… Like, for example, the CDC, we originally had these estimates for 3.5%, 4% case fatality from the WHO. And now, the CDC has on their website… And the data’s still being compiled, but they have more like a 0.26% overall infection fatality rate. Do you think that just is kind of percolated through the public, where…?

And people say… Well, for example, me. I know a bunch of people that have had COVID-19, and thank God, they’ve all been fine. And other people, it has been terrible for. But do you think the public has just sort of gotten a sense that this isn’t quite…? It’s very serious. It’s not the flu, it’s a big deal, but it’s not Ebola. And so, therefore…

Dr. Theoharides: Correct, correct.

John: Yeah.

Dr. Theoharides: No, you’re right. Actually, you’re right. In fact, China has said this for a while. Their mortality rate was less than one percent. I don’t remember if it was 0.2%, 0.8%, whatever it was. The WHO called it a little higher. Here in the States, we called it three, four percent, whatever, much higher. But a problem that has a reason. And now, it’s been discussed, even… And Italy considered it, because I have a few good friends in Italy. And in fact, I’ve been an outside or external advisor for grants for the Italian government, research grants, not only about COVID-19. And this came up recently about COVID-19, as well.

The question has come up many times, “Who do we call “died of COVID-19?” Let’s say someone dies because of a heart problem. And because we’re testing everybody, he or she was tested and turned out to be positive. Well, that doesn’t mean that they died because of COVID-19. They died of whatever they died, but they happened to be positive. It’s like… God forbid, let’s say I die and they test me, I have antibodies against coxsackie. Because I was exposed when I was seeing patients in the clinic and someone with coxsackie, and now, I have antibodies against coxsackie. That doesn’t mean to say I died because of coxsackie, though, okay?

So if we were to take… If we were to create two categories of those, with strict criteria, that died because of SARS…however one defined the COVID-19 disease, those who happened to die, but they were positive. Then, I think we will lose about half the cases, from what I hear.

John: And it’s… There are people out there who have said, and then, you have to bump that number up a little bit, because there are people that died at home that were undiagnosed, and etc. So there’s a…

Dr. Theoharides: It [inaudible 01:09:29] itself, but clearly, it’s not what we thought. But on the other hand, maybe it wasn’t that bad, whether it was intentional or accidental, because everybody was using simulated models to scare people. Because by scaring people, you take some more precautions. So I’m not sure I want to necessarily point the finger, you know, should we have? But now, we have to come out with the facts. We cannot just stay with what we thought it was.

And the kind of conversation we’re having, I dare say, I don’t even hear it on major channels. If we go into Fox, ABC, NBC…I just don’t see it. Everybody keeps on repeating the same questions, the same clichés, the same everything.

John: It’s terribly frustrating. And what it’s devolved into, it’s devolved from a public health awareness campaign…which is what it should have been. The thinking, en masse, evolved… it’s devolved into a very political issue. And when it goes to the politics, all you’re going to get is the same thing that we get in any of our public commentary, which is…for the most part, which is two balkanized sets of talking points. And it doesn’t serve anybody, really. It really doesn’t.

Dr. Theoharides: Right. Well, let me just make the following point. And I’m probably going to kick myself in the butt for saying what I’m about to say. But a number of us were asked whether patients with mastocytosis are at an increased risk for COVID-19. Out of 20 people that were asked, all professionals, I was the only one that said yes. And it surprises the hell out of me, because we know that the mast cells is the major immune cell in the lungs.

We know that the mast cells make cytokines…in fact, more cytokines than the macrophages. We know that these individuals have more mast cells. Then, why not say, given those facts, they’re more likely to be at high risk? I don’t understand it.

John: Well, let me ask you this, Dr. Theoharides. My follow-up there is, I think that makes logical… Based on what I know of your research, and being a layperson who kind of studies this. And we report on IL-6 and IL-8, and some of the stuff we do. Would that be something that you can stratify based on where the mast cell issue was? Because my understanding… You mentioned interstitial cystitis. That’s mast cell inflammation in the bladder. Then, you have rheumatoid arthritis, that can be inflammation in the joints. Would that matter?

I mean, would it be people that have asthma, or people that have some kind of localized mastocytosis in the lungs? Or would it just be somebody that has a sensitive immune system across the board from…?

Dr. Theoharides: You’re absolutely right. So let’s stratify it. First of all, if somebody has aggressive mastocytosis, that means he or she has more mast cells all within the bone marrow, because that’s how… The diagnosis, it’s one of the major criteria. But they also have mast cells in the… Typically, we look at them in the spleen and the liver, because they’re enlarged. And you can see them quickly, whether it’s palpation or ultrasound. It’s a little harder to see it in the lungs, unless you actually do biopsy of the lungs.

So I presume the people with aggressive mastocytosis have it in their lungs and everywhere else. So that’s an absolute group for me. They’re a very susceptible group. Then, you get to what we call indolent systemic mastocytosis, where they have a lot more symptoms, but not necessarily more mast cells, unless you have cutaneous mastocytosis, in which case, you can see. However, three different groups, at about the same time… And that was about nine years ago.

Dr. Metcalfe from NIH is chief of the mast cell section at NIH, Dr. Escribano [SP] in Spain, Toledo, and ourselves published totally independently that in indolent systemic mastocytosis patients, the serum level of interleukin 6 tracks with severity of the disease. And we already know interleukin 6 is high and it’s been considered a target molecule for COVID-19. So just taking those three publications from three different groups, well-known, should have been sufficient. And even that doesn’t…didn’t cut it. Then, we’re left with, as you said, bladder mastocytosis, skin mastocytosis, or gut mastocytosis.

Well, if they do not have systemic symptoms, it will be hard to say that they’re actually a susceptible group, even though if you were to tell me, I’d say yes. But if they’re absolutely fine, except maybe from diarrhea…a little bit of diarrhea, etc., I’d probably say they’re not. And then, you get this whole group of people that have mast-cell activation syndrome, where the mast cells are not necessarily more, they don’t necessarily make tryptase or histamine, which is an indicator of mast cells. But they make tons of cytokines.

And in fact, as you know, the mast-cell activation syndrome can be with or without mastocytosis. So about 80% of the people with systemic mastocytosis also have mast-cell activation, because there are about 10% or so that have mastocytosis, but they don’t have any symptoms, really. Or at least, very few symptoms.

John: So the idea is that somebody whose immune… So people that don’t know some of the terminology, I mean, the idea’s that somebody whose immune system is already on high alert, it’s already looking… It already has a trigger finger, it’s already looking for stuff to fire at, you…

Dr. Theoharides: That’s exactly right. You put your finger… Yeah.

John: Yeah. You throw this virus in the mix. And the cytokine activity is already high, and then it just goes absolutely crazy with it.

Dr. Theoharides: Right.

John: Yeah. So the challenge becomes, with these types of conversations with mastocytosis and mast-cell activation, and then also, the one that I found just sort of head-shaking… And you can tell me if I’m wrong, but I thought the Type-A blood conversation… I mean, you have 40% of the population that has Type A blood. And people now are saying out there, “Well, if you have Type A blood, you have to be concerned.” You know, if you have 40% of the population that has Type A blood, and then, you have a 0.26% infection fatality rate and a much lower fatality rate, something’s not jiving there, in terms of the risk.

Dr. Theoharides: It is not. I have no opinion of that. The only thing I can mention…and it might be worth it, actually, for some people to study in the future, is, as you know, the malaria parasite uses an ABC epitope, basically, on the surface to infect. In fact, it’s not exactly right. It uses something called the Duffy…D-U-F-F-Y, basically, site. What I mean to say is that in certain diseases, there might be a propensity for certain microorganisms to infect. Not because of the exact blood type, but because of what might be associated with a blood type, like the Duffy antigen, in the case of malaria. But I have no idea about viruses at all.

John: Yeah, that’s an interesting point. I mean, when we did research for our nutrition platform on the blood-type diet… Because people… When you go…when you’re in nutrigenomics, they say, “Oh. Well, is that the blood-type diet?” And I’m like, “Well, no. Not exactly. But we did find that H. Pylori risk varies based on blood type, and the stomach ulcer…

Dr. Theoharides: Really?

John: …type of stomach ulcer. As well as, supposedly, Type O blood has more hydrochloric acid, by default, than some of the Type A…

Dr. Theoharides: I did not know those. Thank you for telling me. I was not aware of…

John: So, yeah. So no, this has been a… This has been an absolutely phenomenal conversation. I really enjoyed it. I feel very…

Dr. Theoharides: I’ve enjoyed it. Every time we spoke, your questions are very much to the point, and… I don’t know. It gives me an…at least the possibility to discuss where…especially, the with the risk of being closed, it’s harder to do so. And now, even with my colleagues.

John: I think we’re all kind of hungry for some good conversation. And today’s a… You know, we’re all closing down our social circles. Hopefully, that can start to safely broaden a bit. But…

Dr. Theoharides: [Inaudible 01:17:37] open up again.

John: But thank you for your expertise, Dr. Theoharides. Just so much good information, and…

Dr. Theoharides: Thank you very much. stay safe and well.

John: …have a safe summer. Thank you, my friend.

Dr. Theoharides: You, too. Bye-bye.

John: Bye.

Voiceover: The “GeneFood Podcast is our attempt to synthesize the latest developments in the fields of genetics, nutrition, and medicine, and offer you practical tips and stories you can use in your own unique health journey. If you enjoyed this podcast, you can find more information online at

John O'Connor

John O'Connor is the founder of Gene Food, a nutrigenomic startup helping people all over the world personalize nutrition. John is the host of the Gene Food Podcast and a health coach trained at Duke's Integrative Medicine Program. Read his full bio here.

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