Introduction: Coming up on this episode of The Doctor’s Farmacy.
Dr. Leo Galland: How did COVID-19 change your body, impact your physiology? How is that relevant to your present state of health and the health problems that you have?
Dr. Mark Hyman: Welcome to The Doctor’s Farmacy. I’m Dr. Mark Hyman. That’s Farmacy with an F, a place for conversations that matter, and if you’ve ever had COVID and suffered the consequences of post-COVID syndrome or Long COVID, you’re going to want to listen up because we’re going to go deep into this topic today with one of the world’s experts who’s focused almost entirely on this topic since the advent of COVID and has gleaned so many insights from the medical literature about what to do, how to help ourselves, and actually get to the root cause of why we’re so sick after COVID. So many people have it. We’re going to get deep into it.
Our guest today is none other than my mentor and kind of idol in some ways, Dr. Leo Galland. He’s a board-certified internist. He’s a bestselling author. He’s one of the founders of functional medicine and he’s been a pioneer implying the research on gut microbiome in the treatment of patients with complex chronic disease. Leo was kind enough to let me when I was just getting into functional medicine almost 30 years ago visit him in office in New York City. Spent time with him, learned functional medicine, and has been really a great support to me in learning and mapping functional medicine. He really was one of the founders of the originating concepts that now guide so many practitioners and really changed the world of healthcare and medicine.
Since the onset of the pandemic, he’s devoted most of his time in research to COVID-19 and into the education of other doctors and health practitioners into understanding the biology of COVID-19 and post-COVID syndrome. He’s created a whole series of documents and videos on Long COVID syndrome for the public and for practitioners of healthcare, and he’s just a legend. He was educated at Harvard University, the New York University School of Medicine. He got the Linus Pauling Award from The Institute of Functional Medicine for developing the basic concepts of functional medicine and many, many other awards, including the Albert Norris Marquis Lifetime Achievement Award from Marquis Who’s Who for his contributions to medical innovation.
He’s contributed to the world’s medical literature with several dozen articles in scientific publications and chapters, including medical check-up books, and he’s created this section of functional foods for The Encyclopedia of Human Nutrition. His latest publication, Long COVID: Prevention and Treatment, which I would encourage you all to check out. It’s on his website, drgalland.com. That’s D-R-G-A-L-L-A-N-D.com. Leo, welcome to The Doctor’s Farmacy.
Dr. Leo Galland: Mark, thanks so much for having me.
Dr. Mark Hyman: Oh, I was so glad to talked to you about this because you’re one of the most thoughtful physicians I’ve ever met. You take something apart and you look at it inside and out, you try to understand the biology and underlying mechanisms. You were one of the first to really talk about dysbiosis. I think maybe you even coined the term dysbiosis, which is now in medical literature, which you can find on PubMed, which I find really enheartening that we’re starting to see these concepts of functional medicine like leaky gut and dysbiosis as just part of the medical literature where before we were ridiculed for even talking about it. Now, it’s like the era of the microbiome and you were really way ahead of the curve on that.
Just as you’re way ahead of the curve on that, I think you’re way ahead of the curve on COVID and particularly Long COVID, which I think is a major public health issue. When I started looking at the literature, about 80% of people at three months had some residual symptoms of those who were hospitalized, so I think this is a real problem. I don’t know if it’s 10, 20%, 30%, 40%, 50% of people who have Long COVID, but it’s a lot of people have something going on. If maybe you had COVID and you’re suffering, how can someone know if they have Long COVID? What are the most common symptoms, Leo?
Dr. Leo Galland: Well, I think there are two things to really be aware of. There’s what is being defined as the Long COVID syndrome, and that has many different faces to it, but there’s something else that happens with COVID-19. My approach has been not so much to ask the question, “Do you have Long COVID?”, but rather, “How did COVID-19 change your body, impact your physiology, and how is that relevant to your present state of health and the health problems that you have?” The people who… There are people who are really disabled as a result of COVID. Often they get sick with COVID and, in the early days at least, they would get sick and they would not recover. That is, they would partially recover, but they’d go on to stay impaired in their functioning in some way and symptomatic.
More recently, there’s been this phenomenon where people seem to get over COVID. They might even have a mild case, and then over the next several weeks or several months, something else happens. They get another infection and all of a sudden they crash, and the crash may take two forms. It may be that you’re back to having symptoms that you had with COVID, or that you have a whole new set of symptoms that didn’t even seem to be part of COVID. Of course, the symptoms that get attention, as they should, are fatigue, brain fog, and shortness of breath, impaired exercise capacity.
I think the shortness of breath is a phenomenon that I’ve seen a lot of patients with, and it usually goes like this person cannot… is limited in their ability to do things just because their breathing is impaired. They see cardiologists. Cardiologists say, “There’s nothing wrong with your heart.” See pulmonologists, “There’s nothing wrong with your lungs.” The problem there most of the time is that there’s an impairment of circulation to the lungs, which is very hard to measure, and-
Dr. Mark Hyman: It’s like a vascular-
Dr. Leo Galland: … there are only-
Dr. Mark Hyman: … thing, a lot of these that happen.
Dr. Leo Galland: … yeah. COVID-19 is essentially a vascular problem. I mean, it enters-
Dr. Mark Hyman: The major blood vessels.
Dr. Leo Galland: … the virus enters the body, it enters the body through the respiratory tract, but it goes to the blood vessels. It hones there and it creates inflammation of the lining of the blood vessels. That, then, creates a kind of cascade of effects in which blood clotting occurs because the blood vessels… When you have inflammation in the lining of the blood vessels, you start to get activation of the blood clotting cascade.
Then, there’s impairment in flow to different organs, and that happens in the brain and in the lungs. In the lungs, that effect will produce the shortness of breath, and so what you really need is to restore blood flow. It’s not a problem of the lung tissue itself, and it’s not a problem of the heart pumping. It’s the microcirculation, and the same thing happens in the brain. In the brain, the brain is very sensitive to inflammation, and so around the blood vessels you start to get what’s called perivascular inflammation. That really impacts the brain in many ways and is the cause of what I would say are the two major kind of neurologic problems that occur after COVID-19. One is brain fog, and the other are disturbances in the regulation of the autonomic nervous system, this phenomenon called POTS, which stands for Positional Orthostatic Tachycardia Syndrome. That has really become one of the factors that creates disability after COVID-19.
Dr. Mark Hyman: Yeah. Wow, so basically what you’re saying is after you get all sorts of complications like shortness of breath because of how it affects your lungs, brain fog, and headaches and cognitive dysfunction because of how this affects your brain. You get mitochondrial dysfunction, which is your little energy powerhouses where you can’t have exercise capacity and you feel tired and fatigued. It seems to have these long-lasting effects of fatigue, brain fog, exercise intolerance, shortness of breath that persist and that are really difficult to treat and conventional approaches seem not to work that well on.
Then, of course, you’ve got, as you mentioned, this nervous system effect, the autonomic nervous system where you have trouble with standing up and getting dizzy and your heart rate races and you’ve got just trouble functioning. How many people do you think have post-COVID? What is the literature telling us about it? Because I was… Earlier reports were kind of all over the place, but it seems like it’s a persistent problem.
Dr. Leo Galland: Oh, it’s definitely a persistent problem. The estimate is that there are about 20 million Americans right now-
Dr. Mark Hyman: Hmm.
Dr. Leo Galland: … people in the U.S. suffering-
Dr. Mark Hyman: About maybe 10%.
Dr. Leo Galland: … with… Yeah, and it may be higher. See, there’s another complication of COVID-19 that is sort of distinguished from Long COVID, but it is really a post-COVID complication. In the year after having COVID, there is a virtual doubling of the rate of heart attacks, onset of diabetes, high blood pressure, strokes, and the development of some new neurologic or psychiatric disorder, also GI disorders the latest study that I saw.
There are all of these problems that don’t seem to be COVID, but their incidences increased after COVID, and I think that’s a real phenomenon. I think it’s related to what COVID does in your body. This… I’ve been tracking blood clotting, for example, microscopic blood clots, and disturbances in T lymphocyte function, memory lymphocytes, the ones that are involved in controlling viruses, for example, old viruses. I found that there are people who have fully recovered from COVID, and I’m seeing this mostly I’d say in adult men, middle-aged men. They think they’re totally back to normal, but when I look at these parameters, they have evidence of microscopic blood clotting for months after COVID-
Dr. Mark Hyman: How would that show up-
Dr. Leo Galland: … and-
Dr. Mark Hyman: … for somebody? What would be the symptoms of that?
Dr. Leo Galland: Well, actually there’s a panel of tests that Quest Laboratories does. Quest is a national lab-
Dr. Mark Hyman: Like clotting factors.
Dr. Leo Galland: … and you can get them through almost any lab. It’s called… Quest calls it the thrombotic marker panel. Now, you can’t use that name with other labs because they’ll change it, but it’s a measure of four indicators of blood clots. It’s very sensitive, and it’s something that I’ve used for years in trying to evaluate people with certain kinds of chronic inflammatory disorders and chronic fatigue syndrome, but I have never seen as many positive results=
Dr. Mark Hyman: Wow.
Dr. Leo Galland: … since the onset of the pandemic.
Dr. Mark Hyman: Now, what is it actually testing for? What is on that thrombotic panel?
Dr. Leo Galland: It’s looking for evidence that a blood clot occurred and it doesn’t have to be a major blood clot, just-
Dr. Mark Hyman: What are they-
Dr. Leo Galland: … a minor clot.
Dr. Mark Hyman: … what did they analyze in that test? What do they analyze?
Dr. Leo Galland: Okay, they look at… Okay, the three markers that people aren’t familiar with, there’s something called fibrin monomers. These are strands of the fibrin that creates the clot. There are thrombin/ant-thrombin complexes, which thrombin is part of what’s involved in generating the clot. There are prothrombin fragments and prothrombin. All right, there’s a whole cascade of events involving different proteins, and so we look for activation of those proteins.
Dr. Mark Hyman: Yeah, so basically when your blood’s clotting, it has a whole system of clotting, and those factors are part of the clotting system, you can measure when they’re increased, and that’s what that test is doing.
Dr. Leo Galland: Yeah, this is kind of like the smoking gun-
Dr. Mark Hyman: Yeah-
Dr. Leo Galland: … is what we’re saying.
Dr. Mark Hyman: … that’s fascinating. They may not be symptomatic, but they might have these abnormal markers is what you’re saying?
Dr. Leo Galland: Yeah, and I’ve found them persisting for months and months, and that is what’s been… All of the research that’s looked longitudinally at people who were recovering from COVID find that it takes between two and eight, in people who recover and don’t seem to have any symptoms, it takes about two to eight months for different immune parameters and parameters of blood flow to return to normal, even in healthy young people who had COVID.
Dr. Mark Hyman: That’s quite amazing. Yeah.
Dr. Leo Galland: This is not like most other infections.
Dr. Mark Hyman: Yeah, it’s interesting because we think of COVID as a respiratory problem, but it actually is more of a blood vessel disease than it seems like and it affects everything. The things you were talking about, hypertension, diabetes, the gut issues, these are all inflammatory problems, so how does this COVID-19 sequelae happen? Is it because there’s some part of the virus that persists like the spike protein? Is it still activation of the virus at some low level? What is the thinking around how this continues to go on in the body after you recover from COVID, the acute infection?
Dr. Leo Galland: Well, yeah, there are a number of different theories about that, and the concept of viral persistence is a prominent one. The question there is, is it live virus that’s persisting or is it just viral fragments? Now, this is not a new question. I mean, you and I have dealt with this issue in patients with chronic fatigue syndromes and various inflammatory disorders for a long time because it’s clear that there are a lot of people who get infections and once they’ve had the infection, they go on to develop a chronic inflammatory state. I think it’s way more common after COVID-19 than most other infections. That might have to do with a kind of cascade of effects, and what I have on my website in the document, Long COVID Prevention and Treatment, is a graphic that I call The Web of Long COVID.
I’ve been working with this graphic for a little over a year now since the beginning of 2022, and so far it really seems to be the best representation of all of the factors that contribute and that interact to create this kind of spider’s web that we get caught in. I think one thing that happens is the inflammation of blood vessels triggers the clotting phenomena, which involve these tiny fragments in blood called platelets. Platelets are involved in clotting. They clump together. When the platelets clump together on the lining of the blood vessel, they actually transmit signals that get from the inside of the blood vessel to outside the blood vessel where they activate various cells in the immune system. That phenomenon keeps the cycle moving forward.
It’s aggravated by many things and then it impacts on the immune system. The big research question is, to what extent is there just something that triggers the chronic inflammation that doesn’t go away? To what extent is their an ongoing presence of the virus in the body? Actually, I think both occur and sometimes the virus is live, and the main place where it’s living is in the GI tract. Sometimes the virus is no longer live and replicating. They’re just fragments. They may be in the lining of the GI tract, for example. This is really interesting study, which tells us a lot about this phenomenon.
People who were getting routine colonoscopies after COVID-19, when you get a colonoscopy, they do biopsies of the tissue. These were people who had inflammatory bowel disease, so they were doing… but they weren’t symptomatic. They were quiescent inflammatory bowel disease and what these researchers found was that in people who had Long COVID symptoms or post-COVID symptoms, they could identify fragments of the virus in the biopsies. Whereas, people who had fully recovered and had no issues, they couldn’t, so at least for some groups of people the persistence of either live virus or viral fragments in cells of the body, especially in the GI tract, is an important driver of inflammation.
Dr. Mark Hyman: Yeah, so this is really this whole chronic inflammatory process that happens that’s triggered by this persistence of the virus or particles of the virus or some cascade that starts at kind of there’s a feed forward cycle that you can’t get out of.
Dr. Leo Galland: Right, and then there’s this research from Italy that I would love to see confirmed by other researchers, but it changes the whole concept of where that virus may be hiding in your body. The Italian researchers found that the SARS-CoV-2 virus, which causes COVID-19, could actually be isolated from gut bacteria in people who have COVID-19. I mean, we know that when you get COVID, the virus is in your blood, is in your stool. It’s in the GI tract and people will shed it in their stool for weeks and weeks, even after the respiratory part has cleared and they have negative nasal swabs and they may be free of symptoms. The question is, is this because it’s in your body, it’s in the lining of the gut? Or is there something else going on?
These Italian researchers found that if they took the bacteria from people who have COVID-19 and they grew it in culture for… to the point where there were no viable human cells, that they could actually find the live virus there that was replicating. That’s an usual phenomenon, but it’s not unheard of in which a virus that attacks humans or other mammals can also enter into bacteria and become what’s called a bacteriophage. What’s especially interesting about those findings is that the bacteria that are most infected by the virus are the important beneficial bacteria that are also depleted by having COVID-19. I think when we talked about this before, Mark, I mentioned this bacterial species, Faecalibacterium prausnitzii, which it’s a keystone species. It’s anti-inflammatory. It’s a major producer of beneficial short-chain fatty acids in the gut.
They’re not only anti-inflammatory in the gut, but throughout the body and they even help the brain repair and restore itself. This particular bacterial species is decimated in the course of COVID. People who recover from COVID, they have a normalization, a return to normal of the levels of F. prausnitzii. People who develop Long COVID are depleted of F. prausnitzii, and if you look at people at the time when they’re just recovering from the acute infection, the levels of F. prausnitzii and a couple of other species and the production of beneficial butyrate, that is reduced in people who get Long COVID and it’s normal in people who don’t. That reflects something that COVID0-19 is doing in the gut.
Dr. Mark Hyman: You think that people don’t have this particular bacteria and that’s why they’re susceptible to Long COVID? Or is it the COVID that actually interferes with the bacteria that reduces its benefits?
Dr. Leo Galland: Oh, I… Well, that’s the question. Originally, I thought, “Well, because F. prausnitzii is really an important beneficial bacteria that maybe the people that go on to get Long COVID are those who lack it to begin with,” but the more recent data indicates that the level of F. prausnitzii drops at least during hospitalization, while you’re in the hospital. It’s not impaired to begin with. It drops while you’re in the hospital with Long COVID. In outpatients, the people who recover have normal levels. The people who go on to Long COVID don’t. There’s also… This gets into another aspect of COVID. I talked about the blood vessel aspects. There’s this as yet understudied, but important effect in the GI tract where there is a marked dysbiosis associated with Long COVID.
What’s interesting is it’s similar to the dysbiosis that occurs in chronic fatigue and ME/CFSE. There’s a leaky gut, there’s a loss of these butyrate-producing bacteria that are beneficial. There’s also an overgrowth of some toxic bacteria and one that in the study that looked… The one prospective study, it said, “Okay, we’re going to look at the gut microbiome of people who have just recovered from acute COVID and we’re going to see what happens down the road, six months later who has Long COVID and who doesn’t.” The one marker was the loss of F. prausnitzii and the loss of butyrate production.
The other was an overgrowth of a species called Ruminococcus gnavus, and there were a few others, but this Ruminococcus species, actually when I saw that at the same time I found some data indicating that Ruminococcus produces toxins and neurotoxins. The effect of these neurotoxins in experimental animals is to accelerate the rate of age-related decline in brain function. Now, all of the researchers… yeah, so all of the researchers looking at the effect of COVID-19 on cognitive function are basically saying, “It looks like an acceleration of age-related decline in cognitive function.” I don’t believe in age-related decline in cognitive function, by the way, but it does occur now and then.
Dr. Mark Hyman: Being 80 years old, you’re smarter than ever-
Dr. Leo Galland: Oh yeah.
Dr. Mark Hyman: … so-
Dr. Leo Galland: Right.
Dr. Mark Hyman: .. I think you’re doing okay.
Dr. Leo Galland: I don’t think it happens in humans if they’re healthy, but it’s very [inaudible 00:25:19]-
Dr. Mark Hyman: There’s not that many of us left-
Dr. Leo Galland: … so-
Dr. Mark Hyman: … though. There’s not that many healthy humans.
Dr. Leo Galland: Right, so this substance called isolamylamine, which is produced, can do that. What we have basically are the effects of what we’ll call postbiotics. Postbiotics are substances made by gut bacteria. They may be beneficial, they may be toxic, and so you get into an imbalance in the production of postbiotics that occurs with COVID and is probably part of the Long COVID syndrome. That’s another area that really needs to be addressed is, how do we restore a normal, healthy gut microbiome after COVID?
Dr. Mark Hyman: That’s a really important point because I think most people don’t understand how important your microbiome is to your overall health in terms of your immune system, inflammation, cognitive function, mood, so many aspects. What you’re talking about are something called postbiotics, which are essentially metabolites of bacteria. They’re compounds that bacteria produce in the gut that then are absorbed and affect our entire biology, and so we could actually start to measure the relative amounts of different postbiotics.
We can measure the amounts of different kinds of bacteria and we can, like you’re saying with post-COVID, people have a depletion of the good guys and an increase of the bad guys that are producing toxic stuff. The good guys are producing beneficial stuff, like you said butyrate, which is a very important compound to regulate immune function, inflammation. It’s fuel for the gut. It has many, many benefits throughout the body and you need the good bacteria to produce this, so that’s depleted.
Then, at the same time, these toxic bacteria kind of emerge and start to take over, which is driving more inflammation, so it just seems like a vicious cycle. You talk about this web of Long COVID, I think it’s really important and sort of explains why we’re seeing all these inflammatory problems. Like you talk about how people are twice as likely to get diabetes, heart disease, high blood pressure, GI problems, neurologic issues, stroke, neuropathy, psychiatric issues like depression when they have had COVID. That is all can be explained in my mind through this underlying biology of inflammation. Is that how all these conditions are related to COVID-19?
Dr. Leo Galland: Oh, oh, yeah, I think so, and I think the two areas that really need to be focused on the most are the circulatory issues that I mentioned and then the gut dysbiosis. There’s an interesting study. I don’t think the final version has been published yet, but it was called The COVID-OUT Study. It was a large study that looked at people who had acute COVID-19 and who were given three different alternative treatments, that is not standard treatments. One was ivermectin, the second was a drug called fluvoxamine, which is a kind of antidepressant. It was getting a lot of attention as a possible treatment for acute COVID, and the third was metformin, a drug that’s normally used to treat diabetes.
Well, there were no effects of these on the immediate outcome, and they got them for short periods of time, that is fluvoxamine and metformin were only for 14 days, ivermectin for three days. There was no immediate effect on the outcome, but 10 months later, people who had gotten metformin were 42% less likely to have post-COVID fatigue compared to placebo. What is very surprising in this is that fluvoxamine actually had a negative effect long term. People who had gotten fluvoxamine… Ivermectin had no effect. It didn’t on it own and it didn’t interact with the other drugs, but people who had gotten fluvoxamine were more likely to have post-COVID fatigue and people who got both metformin and fluvoxamine, the metformin did not work as well.
There clearly seems to have been some negative impact of fluvoxamine in this particular study. I tried to figure out, “What’s the difference?” Why… When we look at metformin has a lot of different effects on the body, anti-inflammatory effects on the body, but fluvoxamine does also. The one thing that metformin does that these other substances don’t do is metformin is known to impact the gut microbiome. Many of the beneficial effects of metformin in reversing diabetes and improving insulin sensitivity because metformin is basically an anti-diabetic drug, although it also has longevity enhancing effects. A lot of the effects of metformin are realized through the gut microbiome, the giant microbiome, the changes in the microbiome that accompany the use of metformin, and that’s the one distinguishing characteristic, in fact-
Dr. Mark Hyman: That’s fascinating.
Dr. Leo Galland: … that highlights the importance of the microbiome.
Dr. Mark Hyman: Yeah, that’s fascinating, and. I mean, I think there’s so many aspects of our health that are impacted by this virus. It’s quite amazing, and it’s almost like chronic fatigue syndrome, which just affects everything. I had that 25 years ago, you helped me with that, and I think mine was triggered by mercury, but anything that kind of tips the system into an inflammatory state, whether it’s a toxin and virus or infection, can kind of create these long-term, systemwide effects that people kind of treat symptomatically instead of dealing with the causes of it. I think we’re seeing this a lot in medicine and other people are trying to treat it, but they’re using drugs that treat the symptoms and not the cause.
I’d love to sort of dive in a little bit, and we’ve talked about some of the consequences on cognitive function, on these chronic diseases, autoimmunity, developing allergies, chronic digestive issues. This web of Long COVID, I think, helps explain why this is all happening. It’s a little technical, but I’d love to break it down for people because I think there’s this phenomena that happens where we have sort of the tipping point with the virus that actually causes something called ACE2 deficiency where the virus enters your cell.
ACE2 is basically an enzyme that is involved in so many aspects of our health and that causes mitochondrial effects, which are the energy-producing cells, I mean, the energy-producing little organelles inside your cells. That has eight different things that happened after that which cause organ damage. Can you talk about how these eight things are connected, what they are, and when we start to thinking about treatment? How we start to treat this because it’s not necessarily treating all of them separately. It’s understanding what the common themes are and then kind of resetting the system. Would you mind sort of walking us through? It’s in your document-
Dr. Leo Galland: Sure, I’m-
Dr. Mark Hyman: It’s in your Long COVID prevention treatment document on your website.
Dr. Leo Galland: Yeah.
Dr. Mark Hyman: Also, you have a guide for providers called Understanding Long COVID: A Comprehensive Presentation for Health Professionals, on your website. Highly recommend it. It’s a little technical, but you present all of the data, you present all the research. This isn’t just kind of pulling straws out of the air. It’s really deep understanding of what scientists are now finding out that are at the root causes of some of the finding that are at the root causes of some of the suffering that people are having with Long COVID and COVID itself.
Dr. Leo Galland: I’d love to go through that, Mark, because I spend most of my time thinking about it-
Dr. Mark Hyman: Yeah, yeah-
Dr. Leo Galland: … and-
Dr. Mark Hyman: … let’s get into it-
Dr. Leo Galland: … so the central-
Dr. Mark Hyman: … and if I stop, I might stop you to clarify here and there, but I think if I don’t understand-
Dr. Leo Galland: Sure.
Dr. Mark Hyman: … it, most people [inaudible 00:33:29] I’m going to help people to get this.
Dr. Leo Galland: Okay, so look, the central event in COVID-19 is the entry of virus into cells, and in order to enter your cells, it needs a gateway, and the gateway for most cells, not for all cells, is this enzyme called ACE2, which is only discovered around 25 years ago.
Dr. Mark Hyman: Hmm.
Dr. Leo Galland: ACE2 is a vitally important enzyme. ACE2 is like the fire department. ACE2 is like the police. It’s there to correct and rein things in. It’s there to balance your body in so many different ways, and when the virus enters your cells through ACE2, it damages ACE2 and decreases its function. In almost all of the severe complications of acute COVID-19 can be linked to that damage to ACE2, the cytokine storm and the overexhuberant immune responses and the scarring and the fibrosis, and even the blood clotting, the damage to blood vessels, the lost of ACE2 just amplifies all of that.
With the loss of ACE2 in cells, there is also damage to mitochondria, and the mitochondria are these little tiny powerhouses that are responsible for generating most of the energy in your body. It’s a… That’s a pretty complex phenomenon and it’s not always ACE2 deficiency that causes mitochondrial damage, but it’s clear that ACE2 deficit and mitochondrial dysfunction persist for months after. They are part of this disturbance and function that occurs for months after a person recovers from COVID-19. The foundation for the program that I use with my patients that I describe is trying to restore ACE2 activity and mitochondrial function.
In the immune system, mitochondria are especially important in restoring immune function back to baseline to homeostatic conditions. There, strangely enough, it’s the anti-inflammatory response that is most dependent on mitochondria, not the pro-inflammatory response. The pro-inflammatory response actually damages mitochondria and it does it for a purpose. When there’s a lot of inflammation going on, metabolically the immune cells are acting like cancer cells, and you need to bring that… You need to restore mitochondrial function for the restoration of homeostasis.
That’s at the center of the web. Now, disturbances in mitochondrial function and ACE2 create all the strands that go out from there in one way or another, sometimes directly, sometimes indirectly. The first strand is the one that I mentioned. It’s inflammation of the lining of blood vessels, which then contributes to the clotting phenomena, which is the second strand, these microclots. Microclots have gotten a lot of attention. I think they’re important, but you can’t really understand the microclot phenomenon unless you understand that it’s the blood vessels that are promoting the microclots.
Dr. Mark Hyman: Yeah, so the inflammation is driving the clotting basically, right? The inflammation of-
Dr. Leo Galland: Yes-
Dr. Mark Hyman: … the blood vessels-
Dr. Leo Galland: … it’s the inflammation-
Dr. Mark Hyman: … that says, “Hey-
Dr. Leo Galland: … and specifically the inflammation, yeah, and specifically the inflammation at the lining of blood vessels. Then, that begins to attract different kind and impact different kinds of cells. We have an exaggerated response and a dysfunction in the immune system. There are four different types of cells in the immune system that make up the next four strands in the web. One that is very important that we haven’t spoken about, but in people who are really sick and are not responding well, I think it’s critical, those are mast cells. There’s a condition called a Mast Cell Activation Syndrome.
It’s been getting increasing attention certainly in functional medicine over the past several years. Mast cells are these large kind of primitive cells that don’t circulate in the blood. They’re in the tissues, and they release a couple of hundred different chemicals, including histamine. Now, the role of histamine in Long COVID has gotten some attention because the use of histamine blockers, drugs like Pepcid, have been used to treat it, and low-histamine diets have been used if you look online and you go into chat rooms. People will talk about the benefits of low-histamine diets there. There’s this phenomenon of mast cell activation that occurs and it’s very much tied in with POTS and with some of the neurologic dysfunction that occurs.
Dr. Mark Hyman: Mast cells we think of as typically in allergies, right? When you have allergies-
Dr. Leo Galland: Yes.
Dr. Mark Hyman: … your mast cells-
Dr. Leo Galland: Right-
Dr. Mark Hyman: … increase-
Dr. Leo Galland: … that’s-
Dr. Mark Hyman: … and they increase histamine, which then creates this sort of hives and allergic symptoms. That’s what you’re saying happens as part of post-COVID for people?
Dr. Leo Galland: Yes, except that this can happen without hives. Mast cells in the skin, for example, are very different from mast cells around blood vessels. The mast cells around blood vessels or in the GI tract, they react to blood platelets and to blood clotting. Whereas, the skin mast cells don’t, so this whole blood vessel inflammation, blood clot phenomena, that can impact your gut or it can impact your internal organs with no effect on your skin. You might have redness, but you’re not necessarily going to get hives or the more obvious symptoms of mast cell activation. In my experience, I would say that the people who do not respond in a smooth way to the program that I use or who are the most disabled almost always have mast cell activation as what has taken over, and so you have to address that directly.
Dr. Mark Hyman: You mean with antihistamines?
Dr. Leo Galland: Well, okay, so there’s a whole series of things that are done, and what conventional specialists in mast cell activation will do is they’ll start you with an antihistamine, any of the ones that are used, Claritin, Zyrtec, Allegra, and sometimes those are helpful, sometimes they’re not. One of the rules of mast cell activation is that there are no rules. You can… Anything that may help you can make you worse-
Dr. Mark Hyman: Yeah, interesting.
Dr. Leo Galland: … and because the mast cells kind of become like loose cannons in this situation, and you never know what exactly how they’re going to respond and what they’re going to do. You have to go very slowly, very methodically.
Dr. Mark Hyman: How does someone know if their mast cells are going on and activated in their post-COVID phenomena?
Dr. Leo Galland: There are some blood tests that can be helpful and some urine tests, but they’re not very sensitive, so you can have… Certainly we’ll look at plasma histamine. We’ll look at an enzyme called tryptase that’s produced by mast cells, but as I said, there are 200 different chemicals that are produced, and unless the timing is right, you may miss the peak of those chemicals. Ultimately, it is a clinical diagnosis based upon the nature of the symptoms, the pattern, the response to treatment.
Dr. Mark Hyman: You mentioned like four, so that’s one of them. What are the other-
Dr. Leo Galland: Right.
Dr. Mark Hyman: … range [inaudible 00:43:01] cell [inaudible 00:43:01]-
Dr. Leo Galland: Well, then there-
Dr. Mark Hyman: … [inaudible 00:43:02]?
Dr. Leo Galland: … are a group of, yeah, there are a group of white blood cells called monocytes, which have a tissue component that is the monocyte circle. In the tissues they’re called macrophages, which means a large eater, and these are cells that gobble up bacteria and viruses and damage cells. They have important regulatory functions that are definitely imbalanced. I call it, the phenomenon, monocyte polarization, but they’re imbalanced in Long COVID. I think we we can trace a lot of that imbalance directly to the ACE2 deficiency and to some extent to the mitochondrial dysfunction.
It’s not as if… The mast cells need to be treated on their own. The monocyte macrophage polarization, that will usually respond if you deal with the other factors. Then there’s the production of autoantibodies. That involves a type of cell called a B lymphocyte. B lymphocytes produce antibodies. Antibodies are proteins that your body makes to protect itself basically from foreign invaders. I would say I view antibodies like the artillery. They get… The cells themselves are not involved in the combat. The cells produce these antibodies that fly like cannonballs to be involved in the combat.
One of the phenomena that occurs in COVID-19 is the production of autoantibodies, antibodies that recognize your own cells and components of your own cells. There are many reasons why this happens, and part of it is that there are proteins in your body that are similar to the proteins that are in the virus, and so there’s this confusion in the immune system. As many as 20% of people with COVID-19 may be making these autoantibodies. There’s a lot of debate as to how significant they are.
There’s some people because often the autoantibodies kind of need inflammation to be activated. Most of the time, if the inflammation calms down, they’re just there. They’re not doing anything, but there are some people for whom they really become part of the problem. That is aside from calming inflammation, that’s very hard to treat on your own. You’ll need a medical professional to treat that, and probably the most effective treatment that I’ve seen so far has been intravenous gamma globulin, IVIg, which ties up these antibodies.
Dr. Mark Hyman: The antibodies… Specifically you’re giving antibodies with IVIg, so how does that work? You’re giving immunoglobulins and you’re trying to fight the autoantibodies.
Dr. Leo Galland: What they do is they tie up the autoantibodies, basically.
Dr. Mark Hyman: They kind of bind them up.
Dr. Leo Galland: Yeah, they bind them up. See, there’s a complex phenomenon called immune networks in which antibodies recognize proteins called antigens and they bind to them, but in doing that, they can damage your tissues. There can be fallout from that. Also, the antibodies can lead… can themselves act as antigens and stimulate other antibodies against them, and you get this kind of feed forward cycle of antibodies to antibodies, and then antibodies to the antibodies to antibodies. Sometimes that actually helps to control inflammation and damps it down, but sometimes it aggravates the inflammation. It all depends on the specifics of the individual case. That’s a very complex area which no one can navigate on their own. We don’t have the tools for self-care there. However-
Dr. Mark Hyman: You can measure these different antibodies, though, right?
Dr. Leo Galland: Yes.
Dr. Mark Hyman: What are the common antibodies that we see?
Dr. Leo Galland: Well, the one that I’ve seen in terms of what you can measure through a standard lab, the ones that are most common are the antiphospholipid antibodies. Those are significant because they may be contributing. There’s this phenomenon called antiphospholipid syndrome in which you get blood clots, so they may be aggravating the blood clots, but there are other antibodies that are only identified in research labs that… or in highly specialized clinical labs. THere’s like one lab in the U.S. and one lab in Germany that will measure these, and some of these are-
Dr. Mark Hyman: They’re not specific-
Dr. Leo Galland: … antibodies [inaudible 00:48:34]-
Dr. Mark Hyman: … to… they’re not specific to COVID-19, but they’re autoantibodies your body makes.
Dr. Leo Galland: Some of them are. The ones that may be specific to COVID-19 are antibodies directed against ACE2. This was researched done at the University of Arkansas. These were functional, that is they were interfering with ACE2 function and they developed in people who had been hospitalized in almost 80% of people, but in people who had relatively mild infection and were not hospitalized, about 5% of people. They may play a role. However, most of these antibodies are only active if there’s cell damage and inflammation, so if you can calm down the cell damage and inflammation, the autoantibodies don’t make a difference-
Dr. Mark Hyman: Hmm. Interesting.
Dr. Leo Galland: … and that’s one of the goals. Then, the fourth type of cell are the T cells, T lymphocytes. T lymphocytes are kind of the generals of the immune systems. They are the most evolved cells. They have the most complex sets of functions, and there are many different types of T lymphocytes and one type can morph into another. It is very clear that there’s dysfunction of T lymphocytes in COVID-19, but it isn’t clear exactly what… It may not be the same in everybody.
Maybe the most intriguing study that I saw was a study from Northwestern University where they took people with what they call neurologic Neuro-PASC. PASC stands for Post-Acute Sequelae of COVID, it’s another word for Long COVID, and they took people with neurologic symptoms, which included chronic fatigue. I mean, chronic fatigue is often a neurologic symptom. They took people with fatigue, with POTS, with other complications and they found that there was a major impairment of a group of T lymphocytes that are called TEMs, T effector memory cells. These are cells that are really important for antiviral immunity, They remember what you’ve been infected with and they go after the cells that harbor them. They are… T effector memory cells are the cells that keep viruses in check, Epstein-Barr virus, for example.
Dr. Mark Hyman: Yeah.
Dr. Leo Galland: Okay, everybody in the world gets infected with Epstein-Barr virus during the course of their life. It never leaves your body. It stays in a dormant state, actually living in B lymphocytes, and what keeps it normal is the activity of these T effector memory cells. When those cells take a hit, Epstein-Barr virus gets more active. That’s why antibody levels go up. I think there’s a widespread misinterpretation of the significance of increasing antibodies to EBV in people who have had COVID. I’ve seen it even in people who are asymptomatic. It’s a sign that the effector memory cells the T effector memory cells took a hit.
Yeah, and so the B cell memory kicks in to keep the virus under control. It’s a sign that you need to activate, that you need to support T effector memory cells. By the way, they happen to love fat. They love on fat. They run on fat, fatty acid oxidation. They don’t like sugar, those cells, so you need to support them with an adequate amount of fat in your diet. Inflammation likes sugar and cancer cells like sugar, and that metabolic pathway that is activated when the immune cells are multiplying fast and… yeah, that runs on sugar. It’s a complex kind of phenomenon, but when you want to calm it down, you really… you need the fat.
Dr. Mark Hyman: Amazing, so I think I want to soon get into the treatment because we’ve been talking about the cause. I know there’s two other strands of the web that you want to talk about, the viral persistence and the microbial dysbiosis, which we kind of hit on. You want to say anything more about those two? I want to dive into what people can do about this because it is a daunting problem and it caused a lot of suffering and unnecessary suffering in my mind because there are good treatments.
Dr. Leo Galland: Oh, yeah. I think there are definitely things that people can do and, of course, it starts with diet, which is really important. There’s not one diet that works for everybody, but what we know is that the best way to correct the dysbiosis that occurs is with food. The most important components of diet for recovery from Long COVID or from COVID probably are a group of nutrients called polyphenols, bioflavonoids, and related chemicals that naturally occur in plants, in vegetables, fruits, especially berries, herbs and spices, teas. These play an important role in immune regulation, in curating the gut microbiome, and in regulating the kind of nature of the immune response.
A high polyphenol diet is important. I think it’s important before COVID. It impacts how sick you get with COVID, but it’s definitely important in recovery from COVID. Now, there are are some… If you happen to have a mast cell activation problem, you should… there are other types of diets that you may need. One of the characteristics of the people with mast cell activation problems is they’re outliers. That is everything that seems to be helping other people backfires for them. That’s the main characteristic that they have.
They have to be… If you find that that’s happening, that everything that helps your friends actually backfires on you, there are unpredictable effects, you’re very sensitive to a lot of environmental factors or foods and you can’t make any sense of it, look to mast cell activation as being the thing that got triggered that has to be controlled. Patterns of exercise matter.
Dr. Mark Hyman: Yeah, I mean, basically what you’re saying is a lot of conventional treatment is to come before you dive into what we’re recommending. A lot of conventional treatment is pharmacologic-based medications, and they have limited or marginal benefits. What you’re talking about is a whole comprehensive approach is based on a functional medicine framework of, how do we actually get to the root causes of Long COVID, right? The food is, you know-
Dr. Leo Galland: Oh, it’s totally functional medicine. Functional medicine is the only successful way to approach Long COVID because the problem with the conventional paradigm is it works… It says, “Okay, well, what disease do yo have?” It tries to split everything up into disease categories, and that just doesn’t work for lots of chronic ailments, and it really falls flat with Long COVID.
Dr. Mark Hyman: Yeah, so take us through. You talked about the restoring the microbiome with polyphenols, which I think is something people may not have heard before. I mean, we know about probiotics and prebiotics, but all these plant compounds are really important for fostering a healthy gut microbiome. Those bugs, they like to eat fruits and vegetables basically, right? That’s important.
Dr. Leo Galland: Yeah. Well, the term that I use is it curates, it shapes the microbiome, and the other thing, fermented foods. Fermented foods support the activity of these T effector memory lymphocytes, things like sauerkraut, yogurt. Now, of course, and if you have a mast cell problem, you may not be able to eat fermented foods, so that becomes a tip-off. “Okay, I’ve got to go in that direction. I’m in the 5% that has to approach this differently.” Of course, I’m very tuned into people like that because most of the patients that I wind up seeing are the ones that are the outliers and that fall into those categories. Probiotics can be helpful. In fact, there was a study, I think it was an Italian study that used a multi-strain probiotic in people who were hospitalized with COVID-19, and it was kind of a randomized trial.
Some people who were hospitalized got probiotic when they had acute COVID-19 and others didn’t. The people who got the probiotics eight to 10 months later had a markedly reduced level of fatigue. I think there was like a 40 to 50% reduction in fatigue and over an 80% reduction in severe fatigue, so probiotics definitely make a difference in recovery from COVID-19. The one that I’ve used that I like the most for short periods of time is a soil-based organism, that it’s a strain of Bacillus subtilis that it’s B7092. It produces alpha interferon and the virus is very sensitive to alpha interferon.
I will give people that. It’s available in the U.S. under the name Tundrex and it was originally developed in Ukraine actually during the Soviet era. It was never intended to be a long-term probiotic. It’s a short-term, two to four weeks, but I found it really helpful in two settings with regard to COVID-19, one in acute COVID-19, and the other is for people who have GI symptoms after COVID-19, which a significant number of people do. It really helps control the GI symptoms.
Dr. Mark Hyman: Where can people get that?
Dr. Leo Galland: It’s available online, T-U-N-D-R-E-X. I don’t think it’s in stores. I’ve been using it for years, mostly to help people who had been sick with some kind of GI infection. The GI infection got treated, but they didn’t get better. The Tundrex, the Bacillus subtilis 7092, was very helpful in restoring balance in the GI tract so that their post-infectious irritable bowel syndrome, as it’s been called, improved. Other probiotics that may be helpful are Lactobacillus plantaram, which basically is what ferments sauerkraut. Lactobacillus plantaram is the ingredient in fermented foods that helps stimulate these T effector memory cells.
Now, for people who have mast cell activation, there may be specific probiotics that would be helpful that actually reduce histamine rather than create it. Again, we get into if you’re somebody in whom all of the treatments that help other people don’t work for you, you’ve got it. You need to open that door. That becomes… that dominates the web, the mast cell situation. Then, there are two strains of probiotics that have been shown to enhance the growth of Faecalibacterium prausnitzii.
You can’t… There’s no probiotic of F. prausnitzii. You need it right. You can use prebiotics. These are foods that support the growth that are high in fiber or high in certain kinds of resistant starch that support its growth. There are supplements that you can take of certain oligosaccharides, complex starch molecules that support its growth. Those two strains are… it’s a strain of Bifidobacterium, and I listed all of these on the website and another-
Dr. Mark Hyman: People who are listening-
Dr. Leo Galland: … [inaudible 01:02:48].
Dr. Mark Hyman: … that may want to know about what to take and they’re listening to this and wondering, “Okay, how am I going to find these probiotics? Where can I learn more?” Please go to Dr. Galland’s website, drgalland.com, and you’ll see most of this on there.
Dr. Leo Galland: Right. Right on the landing page at the top, there’s this document called Long COVID Prevention and Treatment, and I try to make it accessible to people who are not health professionals. There’s a lot in there, but it tries to… What I try to do is walk readers through the different steps, and also deal with some of the specific problems that can’t be dealt with just by dealing with the fundamentals of the web.
Dr. Mark Hyman: Yeah, so you talk about the establishment of a healthy gut microbiome as a key part of getting better. It’s really what we’ve been doing in functional medicine for a long time is, how do we restore healthy gut microbiome? There’s specific tips you provide in there about specific probiotics and specific prebiotics that can really help to do this in addition to the things we typically normally do. That’s really important. You talk about some of the other ways of addressing this in terms of viral eradication and addressing the antibodies, and so helping some of the problems that we have to treat specifically that are occurring from Long COVID. Can you talk a little bit about that as well?
Dr. Leo Galland: Yeah, sure, so the issue of viral eradication, not everybody has persistent virus in their body, but it’s kind of hard. Right now, we don’t have good tests for determining that-
Dr. Mark Hyman: Uh-huh.
Dr. Leo Galland: … and so there are herbal protocols that I’ve used to try and ensure that the virus has been eliminated from your body as the foundation for moving on with restoring normal function, and there… The Tundrex probiotic is part of that. There’s an Indian herbal formula called Vedicinals-9 I’ve had some very good results with. There are nine different herbs in a liquid form. The main problem with it is the taste, but if you can get past that, it’s really made a difference for a lot of my patients. It deals with aside from having antiviral effects, it deals with some of the strands of the web as well.
There’s a product that was developed in Israel called Tollovid. It’s derived from the Chinese herb called red Gromwell root. It’s been used for thousands of years in China that works very similarly to the drug Paxlovid, and so I’ve recommended that for a lot of people. It’s not as if there’s one formula that actually works for everybody, but that’s true for all chronic conditions.
Dr. Mark Hyman: You’re finding that herbs are very helpful with the antiviral effects, right?
Dr. Leo Galland: Yes. I start… I will often start with… Let’s make sure that the virus is gone. Let’s use the probiotics and these herbs for viral elimination, and then see where you are. While you’re doing that, let’s try to build up healthy gut bacteria with diet and with probiotics and prebiotics. You can compensate for the deficit of butyrate by taking butyrate, which is readily available as a supplement and not necessarily very expensive if use sodium butyrate, for example. Let’s try to restore ACE2 with not only a highly polyphenol diet, but vitamin D, curcumin, and resveratrol. Curcumin and resveratrol are polyphenols that are widely used in functional medicine and among their protective effects is that they help to restore ACE2 activity themselves.
Dr. Mark Hyman: Yeah, they’re also good for longevity, too.
Dr. Leo Galland: Yeah, yeah. They’re good for a lot of things. I find they make the biggest difference early on is they’re really part of the way that I treat people when they first have COVID, and then I try to use a person’s symptoms as a guide. If fatigue is a significant problem, coenzyme Q10 can be very helpful, and other supplements that help mitochondrial recovery, CoQ10, various forms of vitamin B3 niacin make a difference, and especially with energy in the recovery stage.
Dr. Mark Hyman: You can use all the mitochondrial supports like N-Acetyl-Cysteine, lipoic acid, CoQ10, carnitine-
Dr. Leo Galland: Yeah-
Dr. Mark Hyman: … [inaudible 01:08:42]-
Dr. Leo Galland: … yeah, and-
Dr. Mark Hyman: … yeah.
Dr. Leo Galland: … alpha lipoic acid and NAC, N-Acetyl-Cysteine, also support ACE2 because ACE2 really gets damaged with the inflammation that occurs, so I use them frequently at the onset of infection because they’ve been shown to help protect the damage to ACE2 that occurs with the inflammation. NAC is good for the lungs and alpha lipoic acid is good for the nervous system and is one of the standard natural treatments for neuropathies, for damage to nerves.
Dr. Mark Hyman: Yeah, interesting.
Dr. Leo Galland: You get… There are multifunctional benefits of these supplements.
Dr. Mark Hyman: Hmm. You’re basically personalizing the treatment based on what you’re finding in each patient based on their symptoms and the way the mechanism of actions are working with what we described as part of this sort of web of Long COVID. We talked a little bit about diet and high polyphenols, good fats. We talked about sort of limiting sugar. Talked about restoring the gut microbiome, viral eradication. What else do you do for these patients?
Dr. Leo Galland: There’s certain specific problems that people have afterwards that represent around the outside of the web as the organ damage, so certain specific problems people have that are really due to organ damage and dysfunction and which may need to be directly addressed. For example, the shortness of breath due to the loss of blood flow to the lungs. That can be… there are certain specific supplements that may help that, and you want to prevent… I mean, you want to reverse the blood clotting, but Vinpocetine, Vinpocetine is an extract of periwinkle. It’s been around for a long time, mostly used for enhancing brain function and brain blood flow. Turns out that Vinpocetine also enhances blood flow to the lungs, so that is part of the protocol that I use for dealing with shortness of breath in post-COVID shortness of breath. I have a description of a way you can test some of the mechanisms that might be involved in your shortness of breath in there.
POTS is a very big problem in the people that consult me, and with POTS, the first thing, and first of all, you can make that diagnosis yourself. I can’t tell you how many patients have consulted me who clearly had POTS, and there’s a home test that you can do. I mean, you can do it just by checking your pulse. It’s helpful, though, to be able to check your blood pressure at the same time, but just looking at the changes in heart rate and blood pressure if possible that happen when you go from lying down to standing up. You stand leaning against a wall to kind of relax your body for 10 minutes if you can do it. You can’t do it for 10 minutes, it’s really a big problem, but an increase in your heart rate without a drop in blood pressure of 30 beats a minute or greater is pretty strong evidence of POTS.
We want to address that, first of all, with you need a lot of salt if you have POTS. You need to expand your blood volume, so you have to avoid dehydration. Diet has complicated effects on POTS. On the one hand, carbohydrates tend to help fluid retention. Certainly, very low-carb diets pull fluid out of your body that may not be desirable, but eating a high carbohydrate meal causes a lot of fluid to go into your gut. If you eat a high-carb meal and you feel like you’re going to pass out and your POTS gets worse, you probably need to cut back on the amount that you’re eating. There are a number of resources available online for dealing with POTS. One of the things that is really critical for overcoming that is exercise. The problem is you can’t exercise-
Dr. Mark Hyman: Right.
Dr. Leo Galland: … because you get too… you feel too-
Dr. Mark Hyman: It’s a Catch-22.
Dr. Leo Galland: … bad when you exercise. I will often have people start with supine exercise, that is lying in bed using resistance bands as a way to get started exercise and recondition because deconditioning aggravates POTS.
Dr. Mark Hyman: Yeah.
Dr. Leo Galland: The bottom line here, Mark, is that there are really a lot of things that people can do to recover from this condition, and it’s taken a long time for the medical profession in general and even these special centers for… that have been set up to deal with Long COVID to really become comprehensive.
Dr. Mark Hyman: Yeah, so a lot of the traditional, conventional medical centers aren’t addressing all these issues. They’re just treating them symptomatically with medication, but not actually curing them or getting these people better. Do you think these people can get better, people who are suffering from Long COVID can fully recover? Or is this kind of a lifelong thing?
Dr. Leo Galland: Oh yeah, yeah. People… yeah, people can, and I’ll just give you one example of a woman who first consulted me, I don’t know, maybe over… about a year ago, maybe a little longer. No, I’m sorry. Yeah, it was less than a year ago, but she’d gotten married a year and a half ago and she was so debilitated with COVID at that time that she needed a wheelchair-
Dr. Mark Hyman: Hmm. Wow.
Dr. Leo Galland: … just to get through the airport.
Dr. Mark Hyman: Wow.
Dr. Leo Galland: That was Long COVID. About three months ago, she ran a 5K race and-
Dr. Mark Hyman: Hmm. Insane.
Dr. Leo Galland: … had no adverse effects-
Dr. Mark Hyman: Hmm.
Dr. Leo Galland: … but you have to be very careful in building up. There’s this other phenomenon which occurs in chronic fatigue, fibromyalgia called post-exercise malaise. That name actually doesn’t really represent how severe this is. Although exercise and conditioning is critical for recovery, there’s some people who just can’t do it because even normal amounts of exercise will set them back, not just for a day or two, but for weeks or months. I think that phenomenon is the result of nerve damage and there’s been some very interesting research done on that, and so I’m looking into ways of overcoming the nerve damage that creates this phenomenon with post-exercise malaise. IVIg may be helpful there. Oh, but I’m looking into peptide therapy.
Dr. Mark Hyman: Yeah, something I want to ask you about, so just before we close, I want to sort of talk about a few of the things that are out there in the kind of ether which are around peptides, exosomes, plasmapheresis, ozone, things that people are doing that are a little outside the box that seem to be working for people.
Dr. Leo Galland: Right. I’ve been… I think ozone has to be done really carefully because ozone can be… puts a lot of oxidative stress on the lining of blood vessels, and we already have inflamed blood vessels. Hyperbaric oxygen may be helpful and has been shown to enhance mitochondrial function, but I have to say I’ve seen mixed responses to both hyperbaric oxygen and ozone. I don’t have much experience with exosomes, but I have heard reports of benefit. The… One of my patients benefited from exosomes. Really seemed to impact the neurological response to exercise.
As far as peptides go, I think peptides are a very exciting approach to treatment. Of course, this isn’t something you can do yourself. You need a doctor to do it. It may not be covered by insurance. The peptides generally have to come from compounding pharmacies, but right now I’m looking at a peptide protocol for treating the neuropathic, the neuropathy of COVID-19 and other neuropathies-
Dr. Mark Hyman: What are you-
Dr. Leo Galland: … and-
Dr. Mark Hyman: … finding works for that?
Dr. Leo Galland: … I just don’t have enough data.
Dr. Mark Hyman: Hmm. What are the peptides you’re finding hopeful?
Dr. Leo Galland: Okay, so yeah, there are three peptides that I’m looking at, and two of them actually are also useful in dealing with mast cell activation. Two of them are thymus-derived peptides, thymulin and thymosin beta-4. Thymosin beta-4, I really it it. It really seemed… I think it has beneficial effects in the nervous system. I found great responses to it in people who had head injuries, and these just… There are some oral forms. Thymosin beta-4 is available in pill form, but they’re more effective if they’re given by injection, so I’ll use thymulin and thymosin beta-4 by injection.
Then, there’s another peptide called ARA 290, which actually is FDA approved for the treatment of neuropathy. It’s just not really available and relatively expensive, but there have been controlled, randomized clinical trials with it for autoimmune neuropathy which have shown improvement. It’s based on a natural peptide that’s found in the body, as most of these are. That’s one of the things about peptide therapy is they’re all based on natural substances that are important for healing responses.
Dr. Mark Hyman: Yeah, interesting. Yeah [inaudible 01:20:07]-
Dr. Leo Galland: The thymulin… The thymus-derived peptides may also help stabilize mast cells, and then there’s another peptide called BPC-157, which is a mast cell stabilizer that’s available in oral and injectable form. I think that’s certainly a frontier of treatment and I think very promising.
Dr. Mark Hyman: That’s great. Well, it sounds like there’s a lot of things that are available. This is sort of when this first came on the scene, COVID was driving so much suffering through post-COVID and nobody really knew what to do or how to deal with it. You’ve spent the last three years deeply researching this, looking at all the scientific papers and coming up with a set of recommendations and a framework for thinking about it through the Web of Long COVID, and a way of actually addressing each of the aspects of this from the root cause and helping people recover. I’ve seen many people with post-COVID as well, and I’ve seen them recover by using this approach and also by using sometimes things that are a little out of the box.
I know, for example, I had not exactly post-COVID, but I mentioned to you earlier that I had a arthritis develop after I got COVID. My hand blew up and I was feeling really terrible. Then, I had something called plasmapheresis, which is a way of cleaning the blood of inflammatory compounds. There’s a lot of ways to do this. I think people shouldn’t get discouraged. They should feel hopeful, actually, if they’re suffering because by using a functional medicine framework and by looking at these various aspects and finding someone to work with who can help you with some of these other treatments, whether it’s peptides or exosomes or plasmapheresis or even ozone, it can be very, very helpful. It can be very, very helpful. Hyperbaric oxygen as well is great for recovery of a lot of the brain issues.
People suffer, but they don’t need to, and I think your work has really paved the way for a new way of thinking about how to deal with COVID and post-COVID syndrome, which is creating so much suffering, but there is a way out. I think all of this is really in your website, Dr.Galland.com, both a professional guide, which you’ve created for providers, as well as a guide for your average person who can kind of try to figure out how to navigate this because they’re not going to get this from their doctor. Are there any final thoughts you want to share about what we’re learning, what’s next, how we can kind of sort of take what you’re doing and apply it?
Dr. Leo Galland: Well, I think there are a lot of lessons from the pandemic that we need to absorb. I do think that Long COVID is maybe going to be the major public health complication of COVID-19 as it now becomes endemic because the data suggests that that’s not going away. I mean, most people are going to get COVID-19 once a year, and having had COVID before doesn’t reduce your risk of getting Long COVID. I think this is really… I mean, this is a wake-up call to how we create a sustainable healthcare system.
Dr. Mark Hyman: Yeah, yeah, I think you’re right. It really kind of forced us to look at what we’re doing wrong and how to rethink medicine entirely, so I agree. Leo, thank you so much for being on The Doctor’s Farmacy. This has been great. You’re really such a wealth of knowledge and I think we’ve learned so much, and if anybody who’s heard this podcast, you liked it, you’ve learned from it, please share with your friends and family. Leave a comment how you managed to navigate any COVID issues you’ve had or post-COVID syndrome. We’d love to hear from you and we’ll see you next week on The Doctor’s Farmacy.
Closing: Hi, everyone. I hope you enjoyed this week’s episode. Just a reminder that this podcast is for educational purposes only. This podcast is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided on the understanding that it does not constitute medical or other professional advice or services. If you’re looking for help in your journey, seek out a qualified medical practitioner. If you’re looking for a functional medicine practitioner, you can visit ifm.org and search their Find A Practitioner database. It’s important that you have someone in your corner who’s trained, who’s a licensed healthcare practitioner, and can help you make changes, especially when it comes to your health.