Salmonella Biofilms – Extended Version

Salmonella and Curli Proteins

Salmonella and Curli Proteins

SALMONELLA BIOFILMS INSIDE OF US

(Extended Version – Transcript — For Broadcast Audio Version, go HERE)

Overview:  Foodborne Salmonella infections MIGHT pave the way for arthritis, Parkinson’s disease, Alzheimer’s and ALS, according to a  new study about the potential long-term effects of a salmonella infection.  Symptoms of salmonella infection can include fever, abdominal cramps and diarrhea.  Healthy people usually get over a salmonella infection after about a week.  But sometimes, people later develop creaky joints and pain — you know, arthritis.  Why a brief gut infection can lead to long term arthritis has been a mystery.  The  new study  documents how the inflammation of joints and other symptoms of reactive arthritis may involve curly “curli” proteins that cover a salmonella bacteria.  These curli proteins can stick together like velcro, to produce a biofilm.  Even after our bodies vanquish a salmonella infection, biofilms can remain in body tissues.  If the immune system keeps attacking the biofilms, it can inflame our tissues and hurt them.  For more, here’s one of the lead researchers on the new paper.  He’s  Aaron White from the University of Saskatchewan School of Medicine.  White is Chair of Biotechnology at the School of Medicine. 

TRANSCRIPT

SALMONELLA MAKE FURRY, CURLI BIOFILMS

Salmonella have curly curli

Salmonella have curly curli

Aaron White:  So this study came about because Cagla Tukel is at Temple University. She had studied the Curlii protein itself and showed that if you injected into an animal, you get auto immune responses.

Shelley Schlender  So there’s just a lot even in that one sentence, that is fascinating. Let’s start out with the body of a bacteria. I’ve always pictured a bacteria as this teeny tiny thing that looks kind of like a gel cap. You know, it’s just this blob that is kind of smooth on the outside, but in reality it has these proteins that stick out that look a little bit like fusilli noodles. They’re kind of curly.

Salmonella (Microscope View)

Salmonella (Microscope View)

[Yeah. The organisms that a lot of people study in the laboratory are different than the wild type ones. So the ones in the wild are covered in these, like you say, fusilli or pasta-(shaped proteins). Their surfaces are very complex, adorned with proteins and sugars, things that enable them to interact with their world.  Like with our immune system, for example.

Shelley Schlender These little bacteria are not just smooth on the outside. They have what could be antennas. They could have channels coming in.  To the naked eye, under a microscope, it looks like they’re furry. It looks like they’ve got curly hair.

Aaron White That’s very accurate. I’ve been studying what they do for salmonella, enable the cells to stick together. And in the past, we had thought that that only happens kind of outside of an animal or outside of a human like as a way to survive in the environment. (SS COMMENT:  In other words, when the diarrhea caused by salmonella causes the microbes to be expelled back into the world, a curli biofilm helps them survive heat, UV rays from the sun, drying out, etc etc during them time they’re on the ground, in the water, on the surface of a fruit, etc.  The biofilms give the salmonella a way to survive the part of their life cycle when they’re out in the world, waiting for next next time  they can will be eaten and enter a new digestive tract and go through their life cycle once again.)

Curli Let Salmonella Stick Together in "Biofilms"

Curli Let Salmonella Stick Together in “Biofilms”

Shelley Schlender OK, we’re going to get back to how this is involved with creaky joints and maybe Alzheimer’s, maybe other autoimmune conditions like lupus and Parkinson’s disease. But it starts with the fact that these bacteria have this kind of furry curly outside that lets them stick together like Velcro to make something called a biofilm.

Aaron White Yeah, biofilm is a large group of cells that are stuck together and it provides a survival advantage for the bacteria. So they survive better as a group than they do as an individual.

Shelley Schlender:  Does that mean that when there’s a biofilm with a lot of microbes hanging out together, bacteria in this case, they’re harder for invaders to find? They’re protected from the elements. What does the biofilm do for the bacteria?

Curli Biofilms protect Salmonella from drying out when exposed to the elements, such as the sun

Curli Biofilms protect Salmonella from drying out when exposed to the elements, such as the sun

Aaron White So that’s been a major focus of my research, is the function of biofilms. Imagine the bacteria ends up in a situation where it’s very dry. There’s no nutrients. Right? If it was this individual cell, it would be very fragile. But as a group, as a biofilm, they cover themselves in this protective coating. And that’s what Curli is part of.

Shelley Schlender Excuse me. I’m hearing a lot of beeps of e-mail.

Aaron White: You know what that is? Twitter! Because I just joined Twitter. It’s beeping at me.

Shelley Schlender: Is it beeping at you about your article?

Aaron White: Yes.

Shelley Schlender: Oh, my gosh.

Aaron White: Scientists that I know that have been on Twitter for ages. Congratulations. Or people I don’t know.

Shelley Schlender: They’re literally all atwitter about your new study.

Aaron White   Yes.

Shelley Schlender So biofilms are in nature. It’s a little bit like these bacteria form a union or they form a co-operative, so that if it’s too dry, if it’s too hot, they can shelter themselves a little bit by combining together.

Aaron White: Yes, you can think of it as nature’s way to survive better. Many, many bacteria do that.

Shelley Schlender: And they’re not a multicellular animal like a mouse or a frog or us. But it gives them some advantages of cells sticking together. How about the biofilm, the bacteria on the outside? Do they sacrifice their lives?

Aaron White:  There is a bit of that. Originally when we studied this, we thought how ants come together and cross the stream. They make sort of an ant raft.  We thought of that for biofilms in these bacterial cells. There is some aspect, it seems like, of cooperation, but it’s all aimed at survival, to better withstand stresses. Basically, the cells themselves, too, in the biofilm are more stress resistant than individual cells would be if they weren’t in a biofilm.

Shelley Schlender: And so all of that, Aaron White, is happening out in the world, like in ponds, on the surfaces of rocks, in soil. There are biofilms.

BIOFILM SLIME INSIDE OF US!!!!!

Shelley Schlender:  There has been talk among health care professionals and scientists for a long time that sometimes biofilms can form inside of us.

Aaron White You know, in our lungs, in our mouths, even in our digestive tract. Bacteria do need biofilms to help them survive too. You know, when you get a medical device or a catheter put in? Certain bacteria, It’s very accepted and known that they form biofilms on medical devices in your body, artificial joints. That’s a huge problem. Bacteria forming biofilms on the surfaces.

Shelley Schlender Ewww!! it sounds like these things end up with biofilm slime.

AARON WHITE:  “(Biofilms on Medical Implants and Artificial Joints) They’re very hard to treat with antibiotics. Much harder than the individual cells are.  They become a major problem. Doctors have known for many years, 50 years, that the ability of bacteria to stick together makes them more resistant to treatment. They’re associated with hospital acquired infections, those kind of things.”

Aaron White Yes, it’s very accurate. They’re very hard to treat with antibiotics. Much harder than the individual cells are.  They become a major problem. Doctors have known for many years, 50 years, that the ability of bacteria to stick together makes them more resistant to treatment. They’re associated with hospital acquired infections, those kind of things.

Shelley Schlender OK, so we know that biofilms can be inside of people. And when they’re inside of people, does it make it harder for us to detect that the microbe is there or does it just make it harder for us to wipe it out?

Aaron White Harder to wipe it out. You can detect them fairly easily in some case because they’re accumulating greater numbers than they would just as individual cells. But they’re hard to treat.

CURLI BIOFILMS ARE TOUGH AS CONCRETE

Shelley Schlender: Is it like they put a layer of Saran Wrap on themselves or a skin?

Aaron White: Tougher.  Concrete.

Shelley Schlender: Concrete? So these biofilms end up with kind of a concrete layer on themselves?

Aaron White:  Yeah. That’s what’s unique about Curli. They’re incredibly tough, resistant proteins. Hard for your body to break down.

Shelley Schlender: There’s another complication with these. Our bodies make something like Curli.

CURLI BIOFLIMS LOOK LIKE AMYLOID PLAQUES

THINK ALZHEIMER’S :((

Curli Protein artists rendition cc Wikimedia

Curli Protein artists rendition cc Wikimedia

Aaron White This is a complex area to explain.  What is unique and what we come to appreciate about Curli is that they’re a protein called an amyloid.

Shelley Schlender Oh, I know that term amyloid.

Aaron White Right.  It’s is a very characteristic three dimensional structure.

Shelley Schlender That word amyloid comes up with Alzheimer’s disease especially.

AARON WHITE:  “That was sort of the scary part of our research, really was realizing …. that Curli shares the same three dimensional structure as the amyloid plaques that form in Alzheimer’s disease. . . . Scientists, doctors have wondered how … human (amyloid) proteins start to mis-fold and how that process is speeded up. And that’s where the connection to our works comes in. ”

Aaron White Yeah, and that was sort of the scary part of our research, really was realizing, through reading the literature and other papers that were published fairly recently, that Curli shares the same three dimensional structure as the amyloid plaques that form in Alzheimer’s disease.

Human amyloid beta peptide on Wikimedia

Human amyloid beta peptide on Wikimedia

Shelley Schlender Those amyloid plaques in Alzheimer’s disease. There’s been a longtime debate about whether those cause Alzheimer’s or they’re a sign that there’s been brain degradation. Whichever one it is, when they’re present in high numbers, it’s more likely that there’s been brain damage.

Aaron White I don’t claim to be an expert about Alzheimer’s disease. I’m learning about it. So it’s my understanding that these plaques, when they’re in the brain, they sort of cause dysfunction in the brain.

Shelley Schlender There’s the debate about whether or not the amyloid actually generates dysfunction or whether they’re a bandaid that the body puts in as a structure to keep damage from cascading. So there’s lots of questions about it. But there’s no doubt that the amyloid itself is a sign that there’s been stress inside the brain.

Aaron White Right.

Shelley Schlender Our bodies make amyloid. So not just bacteria. Our bodies make this structure that is very similar to the one in the curli proteins in microbes.

Aaron White: The difference is that the human proteins that become amyloids have a normal function, that’s not an amyloid. It’s just that they mis-fold and make these amyloids.

Elderly Man - Wiki

Elderly Man – Wiki

Shelley Schlender I’m going to stop again then, because you just said something else, that the proteins that we call amyloids that are associated with Alzheimer’s disease. We know that they’re a mis-folded protein. There’s something about them is folding that may make it cascade, meaning more and more get made.

Aaron White 7The scary part is how similar the three dimensional structure of curli is compared to these amyloids that are caused by mis-folded human proteins. Scientists, doctors have wondered how these human proteins start to mis-fold and how that process is speeded up. And that’s where the connection to our works comes in.

Shelley Schlender 8:16] OK, so strangely folded curli proteins on a microbe are a good thing for the microbe. It’s a good thing because it helps them stick together and make a skin and protect themselves from all kinds of things. However, the properly folded protein in the microbe looks very much like a protein looks inside of a human when it’s mis-folded and starting to do some things that are associated with a lot of damage.

Aaron White: That’s exactly it. What was so surprising about our paper, why it was such a big discovery is that these biofilms were thought to be outside the body only. So to actually discover some of these things inside the body means there is a greater chance for interactions to occur between these curli proteins and these human proteins which mis-fold.

Shelley Schlender n the case of your study, you weren’t studying what’s happening inside of a human body. You were studying what’s happening inside of the body of a mouse. But it was with these curli proteins that came from salmonella. Is salmonella unique in making a curli protein that is very similar to the mis-folded amyloid in human bodies, or are there other bacteria and microbes that can make this furry outer stuff that ends up looking very much like an amyloid, that’s mis-folded in a human?

LEAKY GUTS AND AMYLOID CURLI PROTEINS

AARON WHITE:  “That’s again, a bit of a scary point. . .”

SHELLEY:  “You keep saying scary and I’m getting scared. I didn’t think I’d be scared talking with you!”

AARON WHITE:  “Escherichia Coli, So E. coli, the most commonly studied bacterium in history, also makes curli.  In their intestines, most people have E. coli.”

Aaron White I guess what what I mean is, maybe scary is the wrong term. But I mean, what makes this more of a generalized, wide scale thing is that  Escherichia Coli, So E. coli, the most commonly studied bacterium in history, also makes curli.  In their intestines, most people have E. coli. I’m not saying that they do made curli, but they have the ability to do it. Plus, there’s other members in normal bacteria that can make curli as well.

Shelley Schlender:  All right. So there’s a fair number of microbes that can make this furry curli outer coating that can look very similar to the mis-folded amyloids that doctors find in the brains of people with Alzheimer’s when they do autopsies. You’ve used this the word scary. Let’s stick with that, Aaron, White, there in Saskatchewan. .

Aaron White: (LAUGHS).

Shelley Schlender: Let’s stick with that word, because are you implying that you started wondering what if a load of these microbes with these curli proteins, if they get into the body too much? What if they do something to how our immune system works, or how our own protein folding works, so that our good proteins say, Hey!  Let’s take an idea from these mis-folded proteins and let’s do that, too!

Aaron White:  Yeah, that’s exactly what there’s a potential for. We end up eating in our diet. A lot of these bacterial amyloids.  If your intestine in your gut is functioning normally, those amyloids never get exposed to anything in our body other than the digestive tract. And the same thing goes for the auto immune responses that we noted in response to Curli. That seems to only happen once the lining of the intestine is breached.

Shelley Schlender:  Well, then you’re telling us, even though there’s some scary implications to this, this has been happening for millions of years in mammals. And usually it works out OK because our digestive tract keeps the curli proteins from filtering into our blood.

Aaron White: Well, into the tissue surrounding the intestine and then, I guess, ultimately to blood. But as scientists, we tend to think of it as more into  what we call the systemic tissues, so the tissues that are outside the intestine.

Salmonella & LEAKY GUT (also known as intestinal permeability)

Salmonella & LEAKY GUT (also known as intestinal permeability)

Shelley Schlender That’s good news, but also not good news because there is a condition that’s been talked about for decades now called Leaky Gut.  (SS COMMENT.  Go to Leaky Gut Medical Sceptics for an overview about why medical groups have said a “leaky gut” is quack science.  Go to Loren Cordain founder of the Paleo Diet, for a viewpoint about Leaky Gut being a real issue for many people.)  A more specific term for leaky gut is intestinal permeability , where proteins from our food don’t get digested into small enough teeny tiny pieces and instead find some cracks to get through that are bigger, and so larger fragments of proteins can get into our other tissues, outside of our digestive tract. You’re nodding as we’re talking.

WE’LL CALL IT “INTESTINAL PERMEABILITY” . . .

Reactive Arthritis Symptom - Red Eyes

Reactive Arthritis Symptom – Red Eyes

Aaron White:  You’re absolutely right. So that’s a problem. It just gives a greater chance that there’s interactions between, quote unquote, bad proteins and human proteins. That’s what was surprising to us in this paper that we published. First of all, that we could detect salmonella biofilms in the gut, but that we know salmonella during its normal infection, like food-born illness, causes mass inflammation in your gut. And that creates sort of a leaky gut syndrome, for a time period, until salmonella is cleared. But during that time, we know that these biofilms are then there, and that the curli proteins are there, and the gut becomes more permeable. And suddenly you have a situation where these curli proteins could easily be leaking out into the tissue surrounding the intestine.

Reactive Arthritis symptoms - feet & hands (dermatology advisor)

Reactive Arthritis symptoms – feet & hands (dermatology advisor)

Dr. Tukel has studied for years now, what happens when you inject Curli into a body and it causes autoimmunity? And so we teamed up because my specialty really is on the biofilms and detection of Curli. She had a lot of evidence that salmonella made biofilms in the body, but she’d never been able to detect it directly. And that’s where I came in and helped to detect it. And so now all the things that she had measured in previous years, we learned could happen in the course of kind of a natural salmonella infection.  The biofilms were there, plus curli proteins cause these autoimmune reactions. In this case, arthritis, which is again, a surprise.

HEALTHY GUT

KEEPS CURLI PROTEINS OUT OF BODY TISSUES

Shelley Schlender:  Let’s hold onto the fact that you have said that the good news is that a healthy gut that is not leaky is likely to keep these microbes and their curli proteins from going into the bloodstream.

Aaron White:  Yeah. And it makes sense from a historical perspective that if our bodies reacted to every amyloid protein we saw, it would be hard to survive. You’re right. It is comforting. And that was, for me, a quite an interesting part of this paper. If the gut is intact and functioning normally, they even restrict the access of these type of proteins to the outside.

Shelley Schlender:  I’m going to give my gut a little pat right now. It’s amazing some of the things her digestion does for us and the reasons to help it be healthy. There has been some thought among some health researchers and maybe some scientists too, or both, that some of the modern practices of how we live do more to mean that there’s cracks in the gut, meaning that more things leak out. There’s foods that people can eat that will mean that the gut is not in as good a repair. There are medications people can take that can mean that the gut tends to have more leaks to it. There’s the stress of pollution. There’s the stress of just stress or not getting exercise. All of these things can affect how healthy the gut is. And there is a rise of autoimmune conditions. And it looks like possibly conditions like Alzheimer’s, that may have some relationship to how healthy the gut is. Are you shaking your head going? Yeah, I’m listening to you. Or are you shaking your head going? I agree.

SALMONELLA INFECTION

LETS CURLI LEAK THROUGH

AARON WHITE:  “You probably couldn’t pick a worse protein from salmonella to be inside your body.”

Aaron White:  So to put it put this in perspective. And I’ve thought about this for maybe the last six months, to a year, as our paper’s in different stages of getting reviewed and then published, you probably couldn’t pick a worse protein from salmonella to be inside your body. Imagine why salmonella makes them in the first place? It’s to stick together and prevent themselves from getting wiped out. So now you’ve got that protein potentially leaking into the tissues surrounding your intestine. And they’re really, really tough. They’re really hard for the body to clear.  In terms of arthritis, maybe these curli proteins can lodge into joints and things like that. And because they’re so resistant and tough, the body doesn’t clear them fast.

Shelley Schlender All right. So they’re hard to scrub away.  I keep wanting to have a Brillo pad somewhere inside my body.

Aaron White:  That’s very accurate way to to think about it. I 100 hundred percent agree with that. That’s the way I think about it, too. If you could scrub them away!  Bacteria making a biofilm to stick together and make themselves hard to eliminate. So Curli is part of that.

Shelley Schlender Is there a possibility that our bodies, when they’re healthy, do have the ability to do good housekeeping and scrub away some of these biofilms on their own?

Aaron White:  Yes, very much. And we probably encounter biofilms every day. Why it’s significant with salmonella is that salmonella has mechanisms to disrupt normal gut function, so they can make greater numbers of themselves. So they sort of disrupt the gut and then take advantage of it at the same time. Even if your immune system is perfectly healthy, salmonella has ways to disrupt that.

Shelley Schlender: Other bacteria do as well.

Aaron White:  Yes.

Shelley Schlender: And when they do that, that means that the gut can be leakier. More stuff can get out. We can’t really hate these microbes, because they’re just trying to get after our hydrogen.  They’re just hungry.

Aaron White: Yeah. Exactly. It’s their life cycle. They invade us. And then salmonella case, food borne illness, pass back out into the environment to infect other animals, other people.

Shelley Schlender: They’re trying to survive.

Aaron White: Yep.

Shelley Schlender: When our bodies are in good enough balance, a little of them survive, but not too many. But we want our bodies to survive.

Aaron White: Yes.

Shelley Schlender; We want to do what we can to minimize the damage they do inside of us. The problem isn’t just that it’s a curli protein.  It’s that there’s often a bacteria coming out with it that’s colonizing some place. And then the Curli protein skin makes it hard to scrub away.  Or concrete, as you say, the concrete of the curli protein makes a biofilm that’s hard to scrub away.   But the body can scrub it away, if it doesn’t have too many other jobs it’s doing it once.  You think?

AFTER BACTERIA DIE, CURLI BIOFILM 

CAN STILL ALARM IMMUNE SYSTEM

Curli Biofilms Hard to Clear Even after Salmonella Die

Curli Biofilms Hard to Clear Even after Salmonella Die

AARON WHITE:  “(Curli proteins) can go into the tissue surrounding your intestine and perhaps lodge away for months. Right?  To joints. Your immune system does recognize curli and react to it. That’s the problem, because they’re such resistant proteins that could persist in your body and then you get an immune response to them.”

Aaron White: Yep, I think that’s accurate. I think the curli proteins, once they’re made, the bacteria, doesn’t necessarily have to be there anymore for them to cause problems, because they’re just so resistant.  So they can go into the tissue surrounding your intestine and perhaps lodge away for months. Right?  To joints. Your immune system does recognize curli and react to it. That’s the problem, because they’re such resistant proteins that could persist in your body and then you get an immune response to them.

Shelley Schlender: That’s another layer of all of this, because now we’re talking about something called autoimmunity. (SS COMMENT:  Actually, he’s not talking about autoimmunity yet.  He’s talking about hyperactive immunity, where the effort to clear out the curli proteins causes a lot of collateral damage in surrounding tissue.  ie, “friendly fire.”).  Even after the bacterial infection is killed, are you saying that our bodies can start to say, oh, my gosh, if we see a Curli protein, we need to fight it!  We need to get rid of it! Even if there isn’t a bacteria underneath it.

Aaron White: They work through something called the innate immune system.

Shelley Schlender:  That innate means that it’s part of the immune system that doesn’t need any training. It just goes, uh-oh, that’s a bad guy. Let’s get it out.

Aaron White:  Exactly. As part of our innate immune system, they recognize certain things that they know are foreign or from the pathogen and they react to them. So this is, again, research done by a Cagla Tukel showing that these curli proteins actually bind to bacterial DNA. And it’s the two of them in complex together that really alarms the innate immune system and causes autoimmunity.

Shelley Schlender: Isn’t it amazing that our bodies can tell that a little tiny thing, teeny, tiny, is not supposed to be in our body? And try to get it out of there. That part’s good. Except for two problems. Immune cell warriors have to push their way in to try to get rid of the bad guy. And when they do that, they can damage the healthy human cells around it, as an example.

CURLI & INFLAMMATORY ARTHRITIS

Creaky Joints

Creaky Joints

Aaron White: Yeah. And that’s one of the major things we found in this paper is this inflammatory arthritis.  The problem on the joints is the immune response to the bacterial protein that’s there causing inflammation in the joints and then pain.  Friendly fire, like you said.

Shelley Schlender:  Yeah. And so somebody who’s had a salmonella infection or a bad bout of diarrhea as an example. And then two weeks later, goes, gosh, my joints hurt.

AARON WHITE:  “… a certain number of people that have salmonella infections or other food borne illness do end up with this long term condition of inflammatory arthritis. And scientists and again, doctors have maybe assumed that that was related to the bacteria. But again, in many cases, they can’t detect the bacteria in the body anymore. So then it becomes sort of a mystery. And that’s where maybe Curli can fill in some of the gaps”

SHELLEY:  “So it could be that even if the bacteria is gone and the doctor looks at someone and says, ‘I’m sorry, but there’s no evidence that you have an infection. So maybe that pain is all in your head.’  Actually, maybe the pain has something to do with the body still fighting the curli proteins.”

AARON WHITE:  “Yes. That potentially leaked out from the intestine into the surrounding tissues, eventually perhaps reaching a point near a joint. And, yes, the immune system responding to that.”

Reactive Arthritis Tongue (Dermatology Advisor)

Reactive Arthritis Tongue (Dermatology Advisor)

Aaron White:  Yeah. There’s a certain number of people that have salmonella infections or other food borne illness do end up with this long term condition of inflammatory arthritis. And scientists and again, doctors have maybe assumed that that was related to the bacteria. But again, in many cases, they can’t detect the bacteria in the body anymore. So then it becomes sort of a mystery. And that’s where maybe Curli can fill in some of the gaps there because it’s such a resistant protein. It’s possible it could be in your body. It persists for months. Perhaps it could explain inflammatory arthritis.

Shelley Schlender: All right. So it could be that even if the bacteria is gone and the doctor looks at someone and says, “I’m sorry, but there’s no evidence that you have an infection. So maybe that pain is all in your head.” Actually, maybe the pain has something to do with the body still fighting the curli proteins.

Aaron White:  Yes. That potentially leaked out from the intestine into the surrounding tissues, eventually perhaps reaching a point near a joint. And, yes, the immune system responding to that. That’s exactly right.

HEALTHY GUTS & HEALTHY IMMUNITY

AARON WHITE:  “Anybody’s immune system is going to clear some of the curli. It’s just whether it clears at all or not.”

SHELLEY:  “… getting enough sleep, eating food that’s good for your body and good for your digestion, doing things to reduce stress. You might actually be helping your immune system in some huge ways.”

AARON WHITE:  “Yeah, absolutely. Keeping it in balance.”

Shelley Schlender:  All right. And as we’re telling this story, that is somewhat scary. It’s also possible that if a person hypothetically could pull out enough stress from the body and let the body go through a full healing process, that the body could get rid of the curli proteins and heal, and the pain potentially might go away.

Aaron White: Yeah, it’s it’s always a battle. Anybody’s immune system is going to clear some of the curli. It’s just whether it clears at all or not. And in certain individuals, maybe it doesn’t all clear. And then they have problems. But then there’s other people where their immune system does clear it all.  I tend to not think of it as they cleared or they don’t. The immune system is always battling and fighting.

Shelley Schlender: The immune system is always battling and fighting. And it’s also always, in a healthy immune system, telling the troops, “It’s okay now. You can go home.” And that’s an important part of the immune system, too. Or, it says to the immune system troops, “It’s okay now. Right now, we want you to put on your medical badge and we want you to go in and start helping repair the tissues.”

Aaron White: Yeah. The ability to activate, but then also just shut itself down and prevent this friendly fire, where they damage the tissues surrounding what they’re actually trying to fight. You’ve got to keep that in check.

Shelley Schlender: Just as a reminder, getting enough sleep, eating food that’s good for your body and good for your digestion, doing things to reduce stress. You might actually be helping your immune system in some huge ways.

Aaron White: Yeah, absolutely. Keeping it in balance.

LEAKY GUTS, CURLI BIOFILMS

AND AUTOIMMUNITY

AARON WHITE:  “The immune system recognizes Curli. But then because of similarities to our own DNA,  it starts to cause auto immunity where it starts to actually fight our own DNA. That’s the problem. That’s the auto immunity.”

SHELLEY SCHLENDER:  “Oh, dear.  There’s been a term among scientists and some other folks for decades called … molecular mimicry.”

AARON WHITE:  “Sure. … It is a case of almost mistaken identity where the Curli complex, the DNA shows similar to other things in our body that then our immune system would target. ”

Shelley Schlender: Let’s go back to these curli proteins that are the furry curly outer shell of a bacteria like a salmonella. There’s another thing that you keep saying, because so far we’ve actually been talking about normal immune response causing friendly fire and all of that. You’ve been using a different word. Aaron White, there at Saskatchewan University. As an expert in immunology, you’ve been using the word auto immunity. That means the body fighting itself on purpose.

Aaron White:  The immune system recognizes Curli. But then because of similarities to our own DNA,  it starts to cause auto immunity where it starts to actually fight our own DNA. That’s the problem. That’s the auto immunity.

Shelley Schlender: Oh, dear. There’s been a term among scientists and some other folks for decades called 3-way molecular mimicry.   (SS COMMENT.  April 2000 Science Paper from Loren Cordain about how gut inflammation may be part of inflammatory arthritis.)

Aaron White: Sure.  … It is a case of almost mistaken identity where the Curli complex, the DNA shows similar to other things in our body that then our immune system would target.

Shelley Schlender: Something like an undigested protein ends up in the circulation.  The body sees it as similar enough to one of the body’s own proteins. Then The specialized warriors’ that it sends out to really take something out like the T cell warriors, they will go, gosh, that’s the bad guy. And this other one over here looks almost like the bad guy. Let’s just say that’s another bad guy.

Aaron White: Yeah. They can’t tell them apart. I’m not an expert in immunology, Dr. Tukel knows more about that. But that’s one of the next things to look at is the mechanisms behind why Curli actually causes auto immunity and what the process is and the involvement of T cells and things like that. But it is a case of almost mistaken identity where the Curli complex, the DNA shows similar to other things in our body that then our immune system would target.

Shelley Schlender 25:16] And that’s auto immunity. You know, there is some evidence that all of our cells work very hard to say what team they’re on. They have little markers that they send up, little flags that say, I’m part of us, I’m part of our human body. And it’s a specialized tag that should be different from what’s on something like a Curli protein.

Aaron White: Yep.

IMMUNE SYSTEM EYE GLASSES

Ellery Queen with Magnifying Glass

Ellery Queen with Magnifying Glass

Shelley Schlender: If the immune system’s healthy, it has sharp glasses on. It can really tell the difference between those things, as opposed to having poor vision. Maybe the immune system gets too exhausted. It’s still fighting very hard, but it doesn’t have the ability to discriminate and communicate with other cells enough to tell whether that’s really a good guy or a bad guy. So a tired out immune system that’s been fighting something really hard is more likely to make these kinds of mistakes.

Aaron White:  Yeah, it’s, as most things with infection and immune response, there’s many, many factors to it. But certainly that would be one aspect of it, how well they recognize our own molecules as self versus foreign, but also the pathogens that come in. They can turn it upside down, create dis-balance right. And then suddenly know your immune system stats targeting our own tissues.

Shelley Schlender: In auto immunity instead of sending in the medics to say, it’s OK, let’s start repairing things now, let’s cool things off. These exhausted immune system says we’ve got to throw everything we can at this and fight and fight and fight.

Aaron White:  Picking up from there. So now imagine a foreign protein that’s clearly foreign that is really, really hard to clear. So it stays there for a long time. That’s the problem. It’s kind of like this constant stimulus to the immune system, these really resistant proteins that have similarities  to amyloids, which is another aspect, but also persist for a very long time, can trigger auto immune reactions. And that would be fine, maybe, if that was approaching, that could be cleared right away. But if it’s a protein that can persist in your body for a long, long time, it becomes chronic.

Shelley Schlender: And it makes it easier for the body to start to make mistakes about, It looks so much like these other proteins in me, maybe they’re enemies, too.

CURLI PROTEINS AND MANY DISEASES

Aaron White: Exactly. There’s more chance for errors to occur because it’s this constant stimulation of your immune system. It’s doing its normal natural thing. It’s just maybe that proteins aren’t supposed to be there.

Shelley Schlender:  OK. So the paper that you’ve written with that complex title, In Vivo Synthesis of bacterial amyloid curli contributes to joint inflammation during salmonella infection. All of this stems from those observations. And some of this is new, especially the idea that these biofilms of this concretey kind of curli protein could actually be inside the body.

AARON WHITE:  “The discovery (of curli biofilms) inside a body (due to gut inflammation during a salmonella infection) is totally revolutionary for me and my research because it opens up this whole area of interactions with the immune system. And so that was the big surprise.”

Aaron White:  Yeah. That’s. For me, as for somebody who’s been studying the biofilms and the environmental aspects, like how they’re involved in helping salmonella to survive outside of a body, the discovery inside a body is totally revolutionary for me and my research because it opens up this whole area of interactions with the immune system. And so that was the big surprise. I for years thought that these biofilms, you know, we know they’re involved in resistance and persistence. Now, imagining that this might be a normal natural part of a food borne illness, that they form these biofilms before they pass out of the body.

Shelley Schlender:  And it’s one of many examples of ways that something that was inside of our digestive tract can end up in our bodies when it’s really not good for it to be inside our bodies, unless we have a healthy digestive tract to keep them out.

Aaron White:  Exactly. And to be clear, like we need to do more research on this, but I think salmonella is making these curli and these biofilms for its own end to help it survive, As soon as it passes out of the body.  (Ie, getting ready for bright sunshine, dry air, etc on the ground, on water, etc)  It’s just unfortunate that these curli proteins are so resistant, and that they are like these amyloid shape.  Because they can persist and then perhaps leak out into the tissues. It’s almost like collateral damage.  Salmonella doesn’t need to do that. It’s just unfortunate that these proteins just are so difficult to clear and cause these autoimmune responses and potentially even have these interactions with amyloid in our bodies.

Shelley Schlender:  It’s not that these bacteria that are looking for food inside of us are saying, “When we leave the body, let’s be sure that we squirt a lot of curli proteins into the tissue to wreak havoc inside this body just because why not?”  That’s not how they’re thinking.

Aaron White: Exactly. It’s a consequence probably of just the infection. It’s just unfortunate. And that’s what came to me and to Dr. Tukel as we were writing this paper. Like I said, you couldn’t pick a worse protein from salmonella to be hanging around in your body.

Shelley Schlender:  Well, this is a very Canadian attitude. You guys are really live and let live.

Aaron White:  Sure. I just think the ability of Salmonella to make the curli doesn’t really appear to help them in the infection. It doesn’t help them, infect better or anything like that. It seems to me, and to other researchers, that the function of the curlis is to help salmonella survive, probably when they’re outside the body (in the air or on the ground). It’s just that our immune system is exposed to these proteins sometimes, and it does maybe bad things to our immune system.

HOW TO CLEAR CURLI – STAY TUNED

SCRUBBING THE DECKS. (U.S. Navy photo by Mass Communication Specialist 3rd Class Matthew Bookwalter/Released)

SCRUBBING THE DECKS. (U.S. Navy photo by Mass Communication Specialist 3rd Class Matthew Bookwalter/Released)

Shelley Schlender Well, thank you. It’s it’s a fascinating area of research. And there’s two ways that my mind wants to go on this.  One is I wish I could be little tiny, long enough to go and watch all this happening inside the body. It’s so fascinating that these little tiny things we can’t even see, have these complex lives that they’re living. The other part, though, is on the side. That’s my life and the lives of people I care about. How will medical science and healers use this kind of information to see if they can help people be healthier? Could it be that a naturopathic physician would say, clean up your diet, avoid foods that cause intestinal permeability, and somebody who’s in pharmaceuticals would say, let’s find a drug! There will be a lot of different ways, for better or worse, to try to change the fact that these biofilms probably do form inside our bodies.

SHELLEY: “Could it be that a naturopathic physician would say, clean up your diet, avoid foods that cause intestinal permeability, and somebody who’s in pharmaceuticals would say, let’s find a drug! There will be a lot of different ways, for better or worse, to try to change the fact that these biofilms probably do form inside our bodies?”

AARON WHITE:  “I used the term scary. It’s also helpful to learn these things. Because then as scientists and doctors and pharmaceutical companies, at least we will know more the story of why it’s happening.  And then the second you know that, then you can start to work on strategies to stop it from happening.”

Aaron White:Yeah. And, you know, I used the term scary. It’s also helpful to learn these things. Because then as scientists and doctors and pharmaceutical companies, at least we will know more the story of why it’s happening.  And then the second you know that, then you can start to work on strategies to stop it from happening. If you know the molecules that are involved, the proteins involved, like these curli, perhaps then we can think of ways to protect ourselves from them in future. And certainly some of my research will be doing that.

Shelley Schlender: How to protect ourselves from the Curli inside our body. These Velcro like proteins that are on the outside of the shell of a bacteria, and find ways that our immune system can be constructive in how it responds as opposed to overreacting and hurting us more.

Aaron White: Exactly. You know, these types of discoveries that maybe open up a new avenue of interactions that we didn’t even know occurred before. You know, you have a target now. Our discovery is uncovering more to this story, helping us determine better ways to treat autoimmunity or inflammatory arthritis, things like that.

Shelley Schlender: Maybe Alzheimer’s, maybe Parkinson’s, maybe lupus, a lot of different things, possibly have some connection to what you’ve figured out.

AARON WHITE:  “Maybe the scary part is just how similar the structure of these curlis is to the human amyloids that are known to be part of Alzheimer’s and Parkinson’s and ALS and things like that. They’re very, very similar. Knowing that these bacterial proteins, these curli, can persist for a long, long time. We haven’t made that connection yet. But it certainly seems logical from a science perspective that it would make sense that these can potentially interact.”

Aaron White: You know, there’s still lots to be tested and researched. And maybe the scary part is just how similar the structure of these curli is to the human amyloids that are known to be part of Alzheimer’s and Parkinson’s and ALS and things like that. They’re very, very similar. Knowing that these bacterial proteins, these curli, can persist for a long, long time. We haven’t made that connection yet. But it certainly seems logical from a science perspective that it would make sense that these can potentially interact.

Shelley Schlender:  Well, it’s probably too early for there to be a consensus about how to deal with this. But I’ll bet you in your Twitter feeds that you’re getting right now, you’re going to be seeing a lot of ideas.

Aaron White: Yeah, for sure. And because I’m not an expert in these human amyloid diseases, I haven’t really delved into it deeply yet. We’ll be collaborating with other scientists who are experts in these other diseases to try and see if there actually is a link and then perhaps how to slow down the process, if it is happening, lots to think about there.

Shelley Schlender: Well, that would be another two days worth of conversation.

Aaron White: Thank you. My pleasure speaking to you. Really good questions. Yeah, it was good.

Shelley Schlender:  Thank you for the good explanations and thank you for the research.

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Ron Rosedale – Leptin, IL-6 and Cytokine Storms (Extended Version)

Listen here to this extended version of the abridged interview with Ron Rosedale that broadcast on HowonEarthradio April 14, 2020.  Transcript is below.

Host/Producer/Engineer: Shelley Schlender

TRANSCRIPT OF EXTENDED INTERVIEW

Ron Rosedale, MD, Talks about COVID 19, the Immune System and Cytokine Storms

DATE: April 14th 2020

Introduction — The Centers for Disease Control reports that people are at greater risk for Covid-19 hospitalization and often deadly cytokine stoems, if they have pre-existing health conditions, such as high blood pressure, diabetes, heart disease.  Everyone says that healthy eating might reduce these risks – but does healthy mean the New York Times distractibaking comfort foods of brownies and Nutella shortcake?  Does it mean taking dozens of supplements and cutting out fatty junk foods, as Cristina Cuomo recommends for her husband, CNN’s Chris Cuomo?  Up next, we talk with Medical Doctor Ron Rosedale about why he believes that eating and sleeping in a way that reduces high levels of the hormone leptin might reduce the chance of severe symptoms of Covid-19, such as cytokine storms.

This is an interview to help you ask questions about the science behind your health choices.  This is NOT an interview to take the place of medical advice.  Talk with a doctor you trust, if you have questions about your health, and especially if you’re taking medications, and monitor for changes to your need for medications whenever you’re doing a lifestyle change, such as changing your diet.  

TRANSCRIPT

RON ROSEDALE

Can you hear me?

SHELLEY

I’m using the high tech method of recording this phone call on my handheld zoom recorder as you speak on What’s App from India.

RON ROSEDALE

Yes, I am in India.  I’m actually here helping a family known as the Ambani family. Very, very, very prominent. Probably the most prominent, not even probably — they are the most prominent family in India, with their health. And they have they’re mostly located in Mumbai, but ended up getting locked down in a town called Chandigarh.  So that’s where I am in a town north of Mumbai called Chandigarh

SHELLEY

We’ve certainly been thinking about India from here in the United States, because there’s so much concern that India’s population density, meaning it’s in great danger from what will happen with Coronavirus.  On the other hand, there’s also a thought that perhaps India and Pakistan, because they do tuberculosis vaccines, might have an unusual amount of protection.

RON ROSEDALE

Not just tuberculosis, but Malaria. So, you know, malaria is fairly rampant so many people have taken quinalones, chloroquine, things like that, which is being touted as there is a medication to help treat the Coronavirus. So that’s one way of looking at it. 

THE KEY TO FIGHTING AN INFECTION IS A STRONG IMMUNE SYSTEM

RON ROSEDALE

However, the most important thing to fight any infection, especially viruses, is going to be a strong immune system. And that’s really the only way epidemics subside. It’s not that the bug goes away, but that people become immune to it. And that’s especially true for viruses. 

TOO MUCH PROTEIN IN USA; TOO LITTLE PROTEIN IN INDIA

And the problem here in India is that many people have deficiencies that impair their immune system.  So, for instance, whereas in the US, people eat too much protein, which also impairs the immune system, actually, because excess protein is made into sugar. And it raises insulin and it causes what’s called glycation when sugar molecules combine with other proteins and other molecules that impair their function. And antibodies for the immune system are proteins. Protein is very necessary for the immune system. So in the US they eat too much protein, but in India, they eat too little in general, and they don’t have enough protein to actually mount a strong immune system to make antibodies. And so one of the problems with India is a deficiency of protein in general.

MICRONUTRIENT DEFICIENCIES IN INDIA . . . AND THE USA

And then there’s also some micronutrients that are deficient in general in India, such as B12, which found more in animal products. Many people here are vegetarians.  Vitamin D, which people are surprised to hear, even in India. But due to the dark skin, and people who are very modest, so they cover up when they’re out in public, so they’re not exposed to the sun very often, and often it’s really kind of too hot to be outside. And so there’s a gross deficiency in Vitamin D here. And D is very important also for the immune system. And despite having thousands of miles of shoreline, ocean surrounding India. And also because of vegetarianism, they don’t eat very much fish. And so they’re deficient in omega 3 fatty acids, also, which is required to make any new cell, and cholesterol, required to make new cells. So cholesterol is actually a big friend.  They’ve shown that a deficiency of cholesterol also impairs the immune system, which also includes taking cholesterol lowering drugs, oddly enough. Not really, oddly enough. But I guess paradoxically, if you want to call it that. So there’s quite a few immune deficiencies in India.

INDIA – LOCKDOWN — CROWDS MIGHT PROMOTE INFECTION TOO FAST

RON ROSEDALE

And then also, from a societal level, people in India really love to congregate. I mean, they’re very, very sociable people. And so they really crowd together.  They love being with one another. It’s really nice, but not so much when there’s an epidemic going on. I’m not in general in favor of lockdowns, and we can go into why a little while. But in India, it’s a bit of a different story, because if they didn’t have a lockdown, then the first thing people would do is get together in large groups. And that’s kind of good and bad.  A lockdown keeps people indoors, which of course, impairs the vitamin D even more. No sunlight.   

PEOPLE BENEFIT FROM BUILDING IMMUNITY . . SLOWLY, IF THEY CAN

RON ROSEDALE

But from an ideal circumstance, what you want, as we were mentioning, to fight any virus is to become immune to it. So rather than hide from it, ultimately we have to be exposed. You don’t become immune to something unless you are exposed. That’s the whole idea of vaccines, for instance, is that it exposes you to the virus or bacteria that then allows your immune system to build up antibodies to it so that you can fight it. Ultimately, that is what has to occur.

The virus itself doesn’t go anywhere.  It’s going to continue to be transmitted. Every breath people take at this very moment, they’re breathing in some coronavirus. It’s not the Covid-19 that people are talking about. But the cold virus, influenza viruses. They’re everywhere. And the reason everybody doesn’t get sick and die from breathing these viruses is because they’re built up immunity to it. And what is troublesome about the Covid 19 virus that is affecting people around the world right now is that it’s novel. And so there is no path to immunity to it.

SHELLEY

Our bodies don’t yet know how to fight this particular virus. And we’re right now, with all of the lockdowns, we’re buying some time so that we can see if there’s some way that we can medically intervene either through a vaccine or have better testing so that we at least know who has had this virus and who is at most risk for it. And what the general pattern is for how somebody gets sick. There’s so many unknowns that we’re buying at least a little time with the lockdown is my understanding. Does that fit with what you’re thinking, too?

RON ROSEDALE

Partially. I think that the main benefit of the lockdown is, not that we really don’t know who is exposed or getting tested. I think all of that is really not worthwhile. Everybody’s going to eventually test positive to it. Or the vast majority of people will ultimately test positive to it. And the vast majority of people who test positive will have no symptoms because they have a strong immune system. There are certain predispositions, however, that we do know, and that has to do with diabetes, for instance. We know that the vast majority of people who do have a hard time with this virus have respiratory difficulties, have preexisting conditions. One of the prime ones being diabetes, hypertension, previous respiratory difficulty, cardiovascular disease. And I’ll tell you why in a moment, or at least I’ll tell you why. I think that strokes in a little bit.

But the major reason that a lockdown is beneficial is really not to help people as much, but because this virus is so novel, and many people will get sick because nobody has had the opportunity to build immunity to it, that it overwhelms the medical system. And so, so many people are getting it all at the same time, there will be a fraction of those people who will get quite ill that require hospitalization. And the hospitals and doctors can’t handle the onslaught of such a novel virus. And so, so many people reporting to the hospital being sick, many people need ventilators now, if everybody were to get the infection at the same time, that proportion of people who would get seriously ill wouldn’t be able to get the medical care that they need. And so that’s the benefit of a lockdown is to try and get out the frequency of infection so it doesn’t all happen at the same time. It’s really more for medical care. It’s really more for the hospitals and the doctors than actual people, is really how it turns out.

Trying to hide from this virus is probably futile. As I say, the virus isn’t going anywhere. At some point, people have to go outside and breathe. And we know now, in fact, it should have known before. Surprised me that the World Health Organization expressed surprise that when recently it was found that the virus is in aerosol particles when people breathe, it stays in the air for days. I don’t know why there was such a surprise, because that’s what happens with every virus and not even just viruses, but any tiny particle, like pollen, that’s how people get allergies because they breathe in ragweed pollen, because it’s floating in the air, because they’re tiny particles, and that happens with all tiny particles. So one can expect the Covid virus to be in the air and it’s going to stay in the air. And finally when people go outside, they’re going to breathe.  people generally do build an immunity to it. And they’re finding now that the vast majority of people who  test positive, if they were to test the general population, and not just sick people. They’ll find the vast majority of people who do test positive have no symptoms at all, that their immune system is up to the task. It fights the virus, and people don’t even know that they’ve been exposed.

SHELLEY

Most people with Covid-19 might feel somewhere between absolutely awful to a little bit under the weather for a little while. But it won’t be as serious as what we’re hearing about so much in the news about people fighting for their lives in the ICU. And if we get an antibody test, if an antibody test becomes available, maybe people would even know if they’ve been exposed and they might be at less risk for both contaminating other people and also for getting as bad a case of COVID-19 sometime in the future. Still unknowns about whether those two possibilities are there, but they’re more likely if someone could get an antibody test.

RON ROSEDALE

Sure. That would be really helpful because then they don’t have to be scared anymore. They can go out dancing in the street.

EVERYBODY WILL BE EXPOSED AT SOME POINT

RON ROSEDALE

Ultimately, the ideal situation is if people were to get something little micro-doses of the virus so that they do build up an immunity because that’s the only way that they’ll ever survive it.

As I say, almost everybody is going to be exposed at some point. And the real competition is really between building the immune system versus the immune system getting overwhelmed by the virus.  So if we could be exposed to small doses, that’s a good thing. And actually, as I say, in India, it’s a little bit different because people just tend to congregate together. And so a lockdown in India is probably the only way to slow down the spread of the virus, with so many people, and a medical system that just cannot handle so many people being sick at the same time.

But other than that, it’s probably better to be outdoors, because then the virus will just kind of dissipate into the atmosphere. When people do breathe, they will breathe a small dose of it and they will be able to build up an immune system. And some people will get, like you say, they’ll get a little bit sick. Many people won’t get sick at all. They won’t even know they have it.  Some people get a few symptoms. That’s probably, the majority of people get a few symptoms. And then there’s a small percentage of people that will get seriously ill, but only because they have other conditions that impair their immune system or increase inflammation to a great extent.

HEALTHY IMMUNITY Vs CYTOKINE STORM

RON ROSEDALE

I will tell you where, right now, where I think that what the major preexisting condition is and what people can actually do about it. One of the major problems that ends up really killing people and then really, really presenting with the respiratory difficulty, is a mass of inflammation. You know, people have heard of inflammation, where they get swelling due to infection or other things.  And injury, inflammation is there to save your life. Yes. The personal immune system.

SHELLEY
People are starting to hear more about the term, “cytokine storm,” and it’s being described as something that does not happen at the beginning of having a Covid 19 infection. A cytokine storm is more when they’ve had the infection for a little while. They’ve had some aches, they’ve had some other symptoms. And then a little later, it’s as though the body goes into another phase of reaction where suddenly the lungs and other body organs are basically fighting themselves. The term cytokine storm is used quite often to describe this very sudden change, where some people are short of breath. Other people, they’re not short of breath, but their oxygen levels go very far down.  And whatever symptoms they have at that point, it can mean a very life-threatening situation that has to be dealt with, very quickly.

DIABETES, HIGH BLOOD PRESSURE, HEART DISEASE & OBESITY

RON ROSEDALE

Right. And that’s when people need ventilation, when they can’t take in enough oxygen themselves and they need to be hospitalized on ventilators and you’re exactly correct, when you talk about the term cytokine storm. And so here’s what I think ties it all together that I have not read about anywhere. But I think that if I can mention it, maybe people could start researching it. We know that diabetics are very much at risk. People with hypertension are very much at risk. Obesity, obese people are far more at risk. And then there is the cytokine storm that you mentioned.

CYTOKINE STORMS, LEPTIN & IL-6

RON ROSEDALE

Well, there’s a hormone called leptin, and leptin itself is a cytokine.

SHELLEY

What is a cytokine?

RON ROSEDALE

A cytokine is a hormone, essentially, a hormone that acts very locally.  They’re very powerful; most of the cytokines are inflammatory. And so, you know, we hear hormones such as thyroid and insulin and estrogen and things like that. But the body has hundreds, maybe even thousands of other lesser known hormones that don’t necessarily circulate 100 percent in the bloodstream, circulate everywhere, but work more locally.  (NOTE — “Locally” means that instead of being active throughout the body, a cytokine is released within a certain region of the body, such as in your thumb or in your lungs or heart)  And cytokines are sort of like that, although leptin does circulate in general, although it is a cytokine itself. So we know that if you have high levels of leptin, it also causes inflammation. But its major problem is that it elicits the manufacture and the release of other cytokines, one being IL-6. And we know that the major cytokine storm that is occurring with Covid is mediated by IL-6.

SHELLEY

IL-6. That is Interleukin 6. That’s an an inflammatory hormone that the body makes.

RON ROSEDALE

Yes, and it’s very, very inflammatory, and one of the treatments, in fact, one of the main treatments for people with this cytokine storm is to give IL-6 inhibitors, which are given to, for instance, people with bad autoimmune arthritis, for instance, rheumatoid arthritis, which have excess inflammation.  So they give IL-6 inhibitors. So the drug already exists, and is being used to treat the cytokine storm because they know that IL-6 plays a huge role in these storms, and I know the strong connection between Leptin and IL-6.  When most people have too much leptin, they’re hyper leptinemic. They’re leptin resistant. It’s the major cause of obesity. It’s one of the major causes of diabetes, one of the major causes of hypertension. So all of the predisposing factors that we know exist that put somebody at risk of an adverse outcome with Covid-19 (ie, high blood pressure, diabetes, etc), are tied together by excess leptin. And it mediates hypertension and autonomic system dysfunction. So a lot of these people have a difficult time breathing, not just because air doesn’t get in, but there’s a kind of a central way that people’s almost  … wouldn’t say “desire,” because they want to breathe, but they can’t. And not because of obstruction, but because there’s an impairment in their ability to take a breath. And that’s elicited essentially in the brain and hypothalamus. And once again, leptin largely controls the hypothalamus and autonomic dysfunction. And the sympathetic nervous system, vasoconstriction (meaning narrowing of blood vessels), hypertension (meaning high blood pressure). All these things, everything that puts a person at risk for serious disease with Covid has at least partially, if not mostly, to do with leptin. So you want to bring down leptin, and it’s relatively easy.

TO LOWER INFLAMMATION, BRING DOWN LEPTIN

RON ROSEDALE

You can bring down leptin . . .  not totally down to where it should be, because of some of that is mediated by how fat a person is. But what’s not appreciated is that there’s a surge in leptin, a spike in leptin, depending on what a person eats.  So if a person eats a high carbohydrate meal, for instance, it causes  leptin, that day, to perhaps double, from what it would be if a person hadn’t eaten. So we know that if a person asks, for instance, or if a person follows a low carbohydrate, moderate protein, high diet, that I’ve been recommending for 25 years, that leptin levels will really fall. It can probably go to maybe half of what it was prior to having eaten a poor, high carbohydrate meal,  When you lower leptin, I think you can greatly reduce the incidence of inflammation, excess inflammation, cytokine storm, hypertension, all the factors that make surviving this virus far more of a challenge. But this is not recognized. So people go into hospitals, and they get glucose, and everything that occurs, everything they eat inside the hospital, all the IVs they take will raise leptin and make surviving this virus far more of a challenge.

So they take medications to reduce the inflammation, they need to eat also to reduce the inflammation, and to reduce leptin and reduce the IL-6 that’s causing the inflammation in the first place.

SLEEP AND LEPTIN LEVELS

SHELLEY

Well, Ron Rosedale, you’ve been giving a lot of information for people to check out about things like leptin, about the role between high blood pressure and high leptin levels, and how the way somebody eats can start to affect the levels of hormones such as leptin.  Evidently how someone sleeps also affects their leptin levels. Leptin levels also tend to be higher if someone’s not getting enough sleep.

RON ROSEDALE

Sure.

SHELLEY

HOW FAST CAN LEPTIN LEVELS BE LOWERED SAFELY FOR COVID-19

SHELLEY

If somebody has suddenly found out that they have symptoms of Covid-19? Is that too late to start sleeping more, and eating in a way that lowers leptin levels? Would it be stressful to the body to shift to these lifestyle changes?

RON ROSEDALE

No. Well, there is a transitional period, and that’s a great question. In other words, whenever the body, kind of shifts gears, then there is somewhat of a stress put on the body, but probably not near as much of a stress as, for instance, a high carbohydrate meal would be caused in raising leptin and raising insulin. And a meal like that raises leptin within hours. And when it raises insulin and raises leptin, we know that it almost immediately increases so-called sympathetic nervous system activity. Basically, the fight or flight stress. And so it’s not a mental stress, but it’s a physical stress.

And you mentioned sleep. One of the major reasons, and probably the major reason why a lack of sleep raises leptin is because of lack of sleep causes an increase in the sympathetic nervous system to keep a person awake. In other words, it causes secretion of adrenalin and noradrenaline from the adrenal glands to allow the person to stay awake when they ought to be sleeping. And that raises the blood sugar. And then the raising of blood sugar, raises insulin and raises leptin, which increases sympathetic nervous system activity, which also then secretes glucose. And you’re into a vicious cycle.

And we know, for instance, and they did this to college students who will pretty much do anything for some meals. They kept college students up for several days straight. And the vast majority of them actually clinically became diabetic. The diabetes was able to be reversed with sleep.  But it just shows the power of lack of sleep in causing an increase in blood sugar. That increase in blood sugar is due to an overabundance of adrenal hormones, the stress hormones — hormones of stress, such as adrenalin, cortisol, noradrenaline, things that raise blood sugar. And a lot of that is also then mediated by leptin. And it also raises leptin, again, as I mentioned, a vicious cycle also, with insulin . . . throw that in there also.

SHELLEY

Well, Ron Rosedale with as much as you’re mentioning stress adding to a dangerous situation, we should try to think of a joke to tell right now. But I’m a little short on jokes at the moment!

LOWERING LEPTIN & OVERMEDICATION

SHELLEY

Many Americans are on many different kinds of medications for high blood pressure, for high cholesterol, for diabetes, including insulin or insulin lowering medications. When somebody starts to eat and sleep differently, their need for those medications can start to change, so that they can suddenly become overmedicated very quickly. If somebody is not used to eating in a way that lowers leptin levels, would it be best if they work with a medical doctor to help them adjust their medicines?

MONITOR BLOOD SUGAR & DIABETES MEDS

RON ROSEDALE

I’m really glad you brought that up, because medicines do have to be adjusted, because this is not something that takes days or weeks, but can occur almost immediately, like within hours of changing to a low-carb, high fat, adequate protein diet. So yes, when people bring down their leptin, then they bring down their insulin because of the change in diet again, and again, bringing down insulin and bringing down leptin can occur in one day.  Leptin before insulin, actually.  It generally does certainly lower fasting blood sugar. So if they’re on diabetic medications, those diabetic medicines have to be lowered. Many diabetics measure their own blood sugar. So that’s easy when your blood sugar start falling. You take less medication. They can probably do that themselves. Great if they can do it under a doctor’s supervision.

Many doctors don’t understand basically the power of diet in reducing insulin and leptin and therefore blood sugar. But great if it can be done under a knowledgeable doctor’s direction.

MONITOR BLOOD PRESSURE & MEDS

RON ROSEDALE

The other thing that you mentioned is hypertension, and blood pressure, more often than not, probably at least 75, 80% of the time, will come down fairly rapidly when one drops insulin and leptin, not the least of which is because it reduces the sympathetic nervous system activity, which causes vasoconstriction, constriction of blood vessels and fluid retention, which causes an increase in blood pressure. And so by reducing insulin, which allows the release of retained body fluid, so like when people go on a diet, they know, well, you’re losing a lot of water weight. Yes. You’re urinating away retained fluid, but you’re also then dilating arteries.  When this happens, the blood pressure can come down very rapidly and quite significantly. That does also entail a reduction in blood pressure medication.

GLUCOSE MONITOR & BLOOD PRESSURE CUFF

And so, I would encourage anybody who was on to quite a few medications for blood pressure or for diabetes or anything like that, to home monitor.  Get a blood pressure cuff, measure your blood pressure, and as your blood pressure comes down, you can start reducing your blood pressure medication because you can’t wait for a doctor’s appointment, especially at this time when there’s so many lockdowns. So people are going to have to start taking their own responsibility for their health. Many times they’ve been told not to. And so it’s not people’s fault. But everybody wants your doctor to be in charge. And that would be great if they were available, that if they actually knew about such things. But because many of the measurements can be done by people themselves, at home, with blood pressure cuffs, with glucose monitors, it’s relatively easy to measure these things and then recognize that they will not be doing themselves harm.  And in fact, doing themselves a lot of help if they can reduce the medications that they’re on, many of which have adverse side effects.

“COMFORT FOODS” DURING COVID-19

SHELLEY

There does seem to be a strong correlation between people with underlying conditions and having a more serious case of Covid-19 when it does arrive. And yet, I have to say that Ron Rosedale, what you’re describing, even though it’s much more well-known, this topic of a ketogenic diet or a low carb, high fat, adequate protein diet, or even just cutting out a lot of the junk food that people eat, the kind that’s sweet and comfort food . . . ice cream.  What you’re saying is not quite consistent with people do in a time of crisis and worry.

RON ROSEDALE

Yeah, and that’s unfortunate. There’s a lot of misinformation out there, especially when it pertains to chronic diseases like heart disease and diabetes and obesity and autoimmune diseases. In fact, I would say that the vast majority of what people have heard about these things is absolutely wrong. And we can see where it’s  leading to, you know, heart disease is on the rise. Cancer is on the rise. Lifespan now is going down for the first time in human history.  The deeper science that has come out about diet and nutrition over the last 30 some years that I’ve been talking about, this supports the notion that you need to keep insulin and leptin down so that a person becomes more insulin and leptin sensitive. That then allows the burning of fat as opposed to sugar. 

BURN FAT, NOT SUGAR

RON ROSEDALE

Nutrition itself can boil down to in a very, very simple sentence. Nutrition, health in general. And if I had to integrate literally tens of thousands of research articles that I’ve read, it can boil down into a single sentence. That is that a person’s health and longevity is going to be determined most by the proportion of fat versus sugar that they burn over the lifetime. You can essentially burn two fuels, you can burn fat or you can burn sugar or you can burn products of burning fat, such as ketones. And if you burn fat and ketones as your primary fuel, most of the time, you’re gonna be quite healthy. Your incidence of diabetes and cancer and obesity and hypertension, autoimmune diseases, all of the so-called chronic diseases of aging, and even aging itself, are going to be much reduced. Whereas if you’re burning sugar, most of the time, it will be the opposite. You’re going to be much more disease prone.

Sugar was never meant to be a primary fuel.  The reason we have glucose in the blood is not to burn it on a continual basis, but as an emergency fuel because it can be burned without oxygen. So it’s an anaerobic fuel. So if we had to run away from a lion or a tiger and we’re sprinting and we can’t breathe oxygen fast enough to be able to burn fat, then we have sugar because you can burn sugar without oxygen, whereas you need oxygen to burn fat. So it’s a kind of an emergency turbo charged fuel that is there for just that —   anaerobic emergencies. But because people constantly eat sugar–by sugar, we’re talking about also foods that turn into sugars, like all of the carbohydrates and starches that people eat, bread, pasta, cereal, potatoes, rice, all of that. 

You know, we call them different names and even we even call it complex carbohydrate and think that it’s good for you. But as soon as you chew it and swallow it and initially digest it, it all turns to glucose. It’s your cells that actually do the eating. So we think of ourselves as putting food in our mouth, chewing it, and we’re eating. But we’re not, we’re just processing the food, ultimately making little molecular pieces out of it so that we can feed ourselves. So whether it starts out as as rice, potato, cereal, and then we put it in our mouth and we chop it up into smaller pieces and swallow it and then we we basically chemically “cook it,” and we make it into even smaller little molecular pieces to feed our cells, who actually do the eating, what they’re going to see is glucose. And so that’s what we’re feeding them.  We’re feeding them glucose.

It doesn’t matter what our perception is, when we put it in our mouth. While it circulates, and it’s glucose, it also raises insulin and raises leptin, and our cells then  become bombarded with insulin and leptin, day in and day, out almost 24 hours a day. Ultimately, the signal, the really critical, life-giving signals of insulin and leptin become corrupted because they’re overused. It’s like being in a smelly room too long. Pretty soon you can’t smell it. And so there’s you know, there’s reasons for this. And so people become insulin and leptin resistant. And that produces even more insulin and leptin because the body wants to get those life-giving messages heard. And so it produces more insulin and more leptin. But the problem there is that there’s an orchestration, whereas, for instance, with insulin, we want your liver to essentially get a higher signal than your fat. But as you become insulin resistant, your liver becomes resistant first, and then it can’t hear insulin’s message. So it makes too much sugar, so diabetics wake up in the morning, haven’t even eaten, and their blood sugar goes up rather than down. And that’s because the liver has made too much blood sugar, because it can’t hear insulin, because it’s insulin resistant, and the orchestration of insulin becomes corrupted. And so the fine orchestration of signals in the body becomes impaired. That’s what causes disease.

SHELLEY

A new novel virus such as coronavirus-19. adds another way to make a lot of noise in the whole system.

RON ROSEDALE

Absolutely

COVID-19, LEPTIN & IMMUNITY

RON ROSEDALE

Something like coronavirus will bring out deficiencies in our health. You know, it becomes very apparent when a person’s immune system is impaired, and the person’s immune system will be impaired when they are leptin resistant and when they have high levels of leptin, which occurs because of that resistance.  Leptin itself, although better known to be a hormone that regulates fat metabolism and fat storage, we know that leptin is elevated in almost all obese people, what is not appreciated is how important it is for the immune system. 

The white blood cells, which are critical to our immune system, have leptin receptors, in other words, leptin signals white blood cells very extensively. And so when a person’s (cells) can’t listen to leptin properly, their immune system is automatically impaired.  So they can’t fight the infection as well. And then in addition to that, what we talked about is the high levels of leptin predispose to this so-called cytokine storm because it makes too much IL-6 to begin with. And leptin itself is a cytokine and is itself inflammatory. So when it’s high, they body’s already too inflamed. And then the predisposition to manufacture and secrete IL-6, which causes even more inflammation, which also then raises blood sugar . . . so you get all these vicious cycles.

So, yes, you want to try and improve your health as much as you can. And your immune system is certainly going to be a huge part of that. And so improve your health in general.  One of the main ways is by burning fat as your primary fuel, as opposed to sugars. And the only way that you can do that is by having leptin and insulin being signaled properly. People have to look at eating as, it has nothing to do with calories.  You want to eat to regulate the hormones, such as insulin and leptin, that then tell your cells what to eat, i.e., sugar or fat. You don’t just, burn what you eat. You have to go through a whole complex symphony of metabolic orchestration that then tells your cells what they should be eating. And they’re the ones that actually do the eating. And that is what your health depends on. So, again, you eat to regulate insulin and leptin that then tells your cells, whether they should be burning fat or burning sugar, which then has a huge amount to do with inflammation in general and health in general and whether you’re going to be able to fight off his Covid virus or not.

SHELLEY

And so you want your body to be able to fight this new virus and figure out the way to fight it. But you also want your body to know when to not OVERfight, not to fight so much that it causes the cytokine storm.

RON ROSEDALE

You don’t want a bunch of collateral damage. You don’t want your immune system to just start flailing around like a berserker with a sword and killing all the people around. You want to specifically kill the Covid virus, not your own cells. And when the immune system is dis-regulated, what you’re getting is a whole bunch of collateral damage. Your own cells die. You’re killing your own cells as opposed to the virus. Obviously, that will not lead to a very good outcome. So inflammation has to be controlled. And we certainly need inflammation to be able to fight anything, any kind of stress. But certainly you need inflammation to fight viruses. And fight bacteria. But again, it has to be controlled properly and to control it properly. Insulin and leptin have to be controlled properly. And to control insulin and leptin properly, you have to eat properly.

OBESITY AND LOWERING LEPTIN LEVELS

SHELLEY

Leptin levels tend to be higher in somebody who is overweight or obese.  Does it take losing 20 pounds to create this protection. What makes this protection more likely is to get enough sleep and to eat in a way that doesn’t push the body into lots of leptin and lots of insulin.

RON ROSEDALE

Yeah. And again, an excellent point, and this is something that is misunderstood, especially by most doctors and even the people who know about leptin. Many people feel that leptin levels are determined by how much fat a person has. And that’s partially true. The more fat you have–most leptin, not all — most leptin is produced by fat itself. And so it’s thought that the more that you have, the higher your leptin and the only way you bring down leptin is by losing weight, and that you can only bring down leptin by losing weight. And of course, that is a many months long process. That’s not true.  Your leptin levels are determined by two factors, not just one, not just by how much fat you have.  How much fat you have kind of sets kind of a baseline level. So if you are fat, you will have a higher baseline level. But that baseline level can dramatically rise, depending on what a person eats for breakfast or lunch or dinner. And that can be controlled, almost immediately.  Change what you have for breakfast, lunch or dinner and you can cut your leptin levels almost half in one day. And that’s been shown for many years. But it seems still to be unknown to people that you can greatly bring down your leptin. And when you bring down your leptin by preventing the big surges, the big spikes in leptin caused by what a person eats, then you increase the sensitivity, you reduce leptin resistance, and when you reduce leptin resistance, you’re allowed to burn fat. And then, over a longer period of time, you start burning your fat, and then leptin goes down even further. That takes a while, but it doesn’t take a while to bring leptin down dramatically. Very quickly, just by changing what you eat, when you mentioned that leptin tends to be higher in obese people, I would actually go a little bit more emphatically with that, and say that leptin, almost always is higher, in overweight and obese people. It’s very rare for an obese person not to have higher leptin.  There are very, very rare genetic mutations that a person might have. But that would be,  probably less than one in a thousand.  So the vast majority of people who are overweight and obese have high levels of leptin. And they can bring those down, as I say, within one day, if they eat properly. They won’t bring it down all the way. You know, they won’t bring it down as far as we like. That would entail some fat loss. But certainly by bringing down the spikes in leptin, you can improve dramatically, very quickly. And then it also then allows you to burn fat, so that over the long haul, you can bring it down even further as you lose your excess fat, especially your visceral fat, belly fat.  It’s the belly fat, we know, that produces a lot of these inflammatory chemicals, such as IL-6, that causes over inflammation and predisposes to diseases such as diabetes and auto immune diseases. And the cytokine storm that you were referring to earlier.

THREE TAKEAWAYS

SHELLEY

If somebody has a higher weight than they think that they should have, or if they’ve been told that their obesity is a is a danger to them, that simply by starting to eat differently, they’re significantly changing the inflammatory response in their body to one that is not going to be as much of a roller coaster, that will probably fight the virus better, but also not create a cytokine storm. There’s three things that I think we could give people as take away points from what you’ve said.

  1. Whatever somebody’s weight, eating a low carb, high fat, adequate protein diet, may have some  protection. If what you say is correct, this way to eat could have protection for people, to help their body fight the coronavirus.
  2. Starting now is probably better than starting in the middle of finding out you have symptoms.
  3. The last is that even though some doctors don’t know about this way of approaching health and wellness, there’s an increasing number of health professionals  who do. And additionally, for anybody that’s on medication, if they can monitor what’s happening with their body’s response to the medicines and let their doctor know, that’s probably important because anybody on medicine will probably see some significant shifts and could be overmedicated very quickly if they don’t let somebody know to help them adjust their medicine.

WORK WITH A KNOWLEDGEABLE DOCTOR (WHO UNDERSTANDS “KETOGENIC” DIETS)

RON ROSEDALE
It’s always best under an educated doctor’s supervision. Right. Somebody that actually understands the changes that occur when a person changes to a diet like we’ve been recommending for decades. So that would be ideal, but  I wouldn’t necessary dependance really. As you say, it depends on the doctor. Totally depends on the doctor. There are some doctors that are very knowledgeable. It would be great to listen to their advice. And there’s other doctors who know very little about this and whose advice actually might be more harmful than not. So it’s really hard to say. But one thing I would urge people is to take their health in their own hands.  Read a little bit about what leptin does. Read a little bit about the power of a low carbohydrate, high fat diet, which now being called a ketogenic diet, which I don’t agree with the name.  It’s not the ketones that are so beneficial, but the actual burning of fat. And don’t be afraid really to adjust your own medications. If your doctor is unable to do so, if your doctor does not really know about the physiology for instance, of insulin and leptin and what it will do to the blood sugars. If your blood sugars fall. You must reduce your blood sugar medication.  Reduce your diabetic medication. It’s really quite simple. Start off slow.   If blood sugar stays high. Reduce it a bit more. Same with blood pressure. If your blood pressure is going down, reduce your blood pressure medication. Don’t be afraid to do it. Great If you can talk to your doctor, and he can, maybe if you’re on multiple medication, he could tell you which medication might be best to reduce to begin with. But if you, for instance, can’t get ahold of your doctor because they’re so busy because of the viral infections that are going around, then take your health in your own hands. It’s not really that hard to do.

SHELLEY

If they do feel like they need a doctor’s advice, if they could start calling today to interview different doctors and find one who they could shift to, who could walk them through this. There’s an increasing number of agencies and places that offer ways to coach people on how to eat in the way that you’re describing.

RON ROSEDALE

Absolutely.  There’s even like online apps that can help people in this sort of thing. So there’s certainly help out there. And a person just has to be diligent and look around. As you say, interview, interview doctors, look at different websites. But I think that certainly the situation right now calls for self  education, you know, educate oneself about what they can do on their own to take their own health in their own hands. You’ll know your health better than anybody. You’ll know what your blood sugars arel you’ll know what your blood pressure is. You’ll know what it is this hour, because you might not be able to call your doctor this hour. So I would certainly recommend a person going and purchasing a blood pressure cuff and a blood glucose monitor. Those are the two indexes that can change quite dramatically when they change their diet and need adjusting as far as medication for sure.

DR. ROSEDALE — HAVE YOU HAD COVID-19?

SHELLEY

Well, good luck with what you are doing yourself. Have you had this virus yet that you know of?

RON ROSEDALE

You mean have I personally?

SHELLEY

Yes, have you had Covid-19 as far as you know?

RON ROSEDALE

No.  I’m actually locked down in a beautiful facility, actually, so I can’t really complain. I’m taken very good care of it. Right now, there’s virtually no chance that I could be exposed. So I have not had it. I actually would like it.  That might sound funny to say.  But I would like a low dose. I would like to actually be exposed to a little bit, because I know eventually I’m going to have to be. And I would just as soon be exposed a little bit so that my immune system would start building up tolerance and building up immunity, building up antibodies and building up white cells to the virus, so that when I do get a bigger exposure, you know, it’s not going to affect me so much. So as I say right now, where I am and I think in India, I don’t necessarily disagree with the advice for a lock down only because in India there are so many people, and the medical system can be so easily overwhelmed. And because the society here is so social. I mean, people just love to congregate, that I think the prime minister didn’t have much choice but to kind of insist on a lockdown to keep people from spreading it so fast that would overwhelm the medical system. But I think in most countries, I kind of agree with the approach, that Sweden has taken, which is just actually go about your business. But pay attention, keep your distance. Wash your hands. Don’t cough on people.  If you have it, stay on there. They seem to be doing just fine. I think that probably for most countries, including the U.S., I think or at least most places in the US, would do probably better, with that approach, than trying a more complete lockdown. In other words, don’t be afraid of getting it. You just don’t want to get a high dose of it. You know, you don’t want people to sneeze on you or you don’t want to sneeze on other people. Or cough on other people.

SHELLEY

And, you know, there is new evidence that indicates that people get the highest, most virulent dose of it. When people are early on in the infection and may not even have symptoms, which is quite a different thing about this virus, that it’s at its most potent when it’s early on, that’s when it’s most likely to be shedding and spreading. Probably an exception is if somebody is in the hospital and having to be intubated for a ventilator. Somebody who’s doing that from a health care perspective is very much at risk because they’re just so close to somebody. But in just general hanging out with people, it’s when people don’t have symptoms, and it’s early on that they’re most likely to spread this virus, which would mean that the more that people get lots of rest and eat, not for comfort, but for health, it might be a smart idea to do those things.

RON ROSEDALE

I think that’s exactly correct. Once again, that the major superpower, I guess, of this virus is that it’s new. So people have not developed an immunity to it. And therefore, early on, like you say, it’s going to be much worse because people have not yet developed an immunity to it. So the more a person has the virus, the more, if they have a good strong immune system that build up antibodies against it that will be able to engulf it and kill it. So then it becomes less virulent, as time goes on in a particular person and then over the weeks and months between people, as people start developing an immunity to it. But early on, when that immunity is lacking, certainly the virus becomes the most contagious and the most powerful because the immune system is not fighting it then.

SHELLEY

Yes. And so here we are in this situation where it would have been so fun to talk with you additionally about what just what is going on. How does the immune system fight things? What is the mechanism of what causes high blood pressure? We could have had a fun conversation about those things, too, but right now what’s on people’s minds is how do they do what they can to protect themselves? How do they do what they can to share information with a loved one that they care about that they’d like to have around in another year? These are real questions that people are facing.

RON ROSEDALE

Yes, absolutely. Well, you know, for me, eating properly is paramount in any disease. But certainly the chronic diseases of which an impaired immune system is one which then can manifest and is brought out by this virus. You want to eat properly.  In addition to eating properly. There are certain micronutrients a person can make sure that they have enough of such as vitamin D. That’s why staying indoors sometimes might be counterproductive because certainly the best way to get vitamin D is to get sunlight. So I would not be afraid of going outside.

And also, as you go outside and you’re breathing, your aerosol particles will dissipate into the atmosphere. So they’ll become less concentrated, whereas indoors they’ll become more concentrated. So being indoors might not actually be the best thing. Outdoors, it’s fine as long as you don’t congregate with people so that, you know, they’re not directly getting a huge dose of coronavirus. Let it dissipate off into the atmosphere. So keep your distance a little bit or. You can take certainly take very easily, Vitamin D soft gels. 

SHELLEY

You still think that outdoors is best. And for people in Colorado where this will broadcast, what a beautiful place to be outside and people are learning to keep their distance from each other during this virus crisis.

RON ROSEDALE

Exactly. I think being outdoors is great. I would encourage it. that the fact that there’s more awareness than it can be an aerosol is why now the Centers for Disease Control is recommending face masks.

Yeah, well, I it actually surprised me more than anything when the World Health Organization a week ago or so was surprised that Cauvin can be in the air for days.   I was surprised that they were surprised because that’s pretty well known on almost all viruses. For instance, influenza is known to be in the air for days. I don’t know why this virus would be any different, but anyway. I would certainly encourage sunlight, encourage open air. Make sure you do get enough vitamin C. I don’t necessarily believe in going overboard with it. There are downsides to taking too much, but something like 500 milligrams or so twice a day or high. I particularly like the form of vitamin C.

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Almost Human – Julius the Chimpanzee Caught Between Two Worlds (FULL INTERVIEW)

Almost Human Julius PhotoAlmost Human – The Story of Julius, the Chimpanzee Caught Between Two Worlds (Extended Version) by Alfred Fidjestøl.  This is the full version of the interview.

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Low Carb Diets and Longevity – Ron Rosedale, MD – Extended Version

credit: healthline

credit: healthline

Low Carb Diets and Longevity – Ron Rosedale, MD – Extended Version  Dr. Ron Rosedale, MD, gives a “second opinion” about a widely publicized report in the prominent medical journal The Lancet.  The Lancet report contends that low carb diets (40% carbs or less) shorten lifespan, and moderate carb diets (roughly 55% carbs) promote longer lifespans. The study is being hailed as proof for why people should “eat carbs in moderation.” But what if the Lancet study didn’t go low enough on carbs to reveal potential benefits of a VERY low carb diet?  Dr. Rosedale advocates a very low carb, adequate protein, high fat diet, meaning roughly 15% of calories from carbohydrates, 15% from protein and 70% from fat.  – Producer – Shelley Schlender

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TRANSCRIPT

Shelley – Ron Rosedale what is it about your background that means that you can be somebody who speaks to the idea of low carb diet and longevity.

Ron Rosedale – For the vast majority of my professional career, that’s what I’ve been studying. And I believe at least in the U.S. I was the first person to actually recommend and utilize a high fat low carbohydrate diet to treat a multitude of the chronic diseases of aging and have been studying the biology of aging for my entire adult life.  So what my interest has been has been in the dietary connection to the hormones and pathways that are known to influence, if not regulate, the biology of aging teeth.  That’s really what one has to look at if one is going to evaluate the health of any particular dietary or interventional regime–how does it affect aging and mortality.

Shelley –  Here is a study that came out recently from the Lancet the journal Lancet about just that topic. That longevity study seems to show that people who eat a low carbohydrate diet die sooner than people who eat moderate carbohydrate diet.

“The problem is, they didn’t study a low carbohydrate diet!” — Ron Rosedale

Ron Rosedale –  Well first of all ,had they stuck to the title of the study, where it’s different amounts of carbohydrates versus mortality, if they had if they had not used, later in the study, the word “low carbohydrate” it would have been a better study because the problem is that they didn’t study a low carbohydrate diet.  So here they are then making conclusions about a low carbohydrate diet, which is you know, picked up everywhere about low carbohydrate diet. And they didn’t study a low carbohydrate diet. Not at all.

Shelley Schlender – In the Lancet study the amount of low carbohydrate that they were looking at was 40 percent or less. You say that that’s not a low carbohydrate diet?

Ron Rosedale – No. They lumped it all into — I think the the lowest quartile was 37 percent. That’s not low carbohydrate at all. In fact that’s probably the worst diet, and that’s what their studies showed. I think the worst diet is one where you mix, kind of, an equal amount of carbohydrate and fat. And the reason it’s the worst is because carbohydrates turn to sugar, then the sugar goes up, and it raises insulin and when you raise insulin, your body can’t burn fat.   If you summarize all of nutritional science you can do it in a single sentence. And that is that, one’s health and lifespan is going to be more determined by the proportion of fat versus sugar that a person burns in a lifetime than anything else. The key is to burn fat. And if you eat 40 percent, or 37 percent carbohydrates, you will not be able to burn fat. That’s why people are getting so fat—people get fat not because they eat fat but because they can’t burn it.

Shelley – What stops them from burning the fat?

Ron Rosedale – When you eat a bunch of carbohydrates, and a bunch to me it would be 37 percent. That’s a lot of carbohydrate. Really. This will raise specific nutritional pathways and hormones. People have heard about insulin and I first started talking about the connection with insulin and disease many many decades ago and now it’s becoming more commonplace. Still, we knew even a quarter of a century ago that when you raise insulin it prevents the burning of fat. And so when you eat carbohydrates, the carbs turn into glucose, you raise insulin and you can burn fat. It’s as simple as that. But you also you also raise leptin and you also raise another even more critical pathway called the target of rapamycin that hardly anybody knows about right now. All of these conspired to make a person store fat and not burn it. And that’s always a awful and that’s where you can run into higher mortality and that’s what this study found.

So what this study really showed was that a medium carbohydrate diet, so a diet that consists of high fat and high carbohydrate or you might say medium-fat, medium-carbohydrate, however you want to say it– there was no low involved anywhere that will be unhealthy. And they found also who they should use for them to eat a very high carbohydrate diet. That’s also very bad. So they found two bad groups. One was a medium carbohydrate kind of medium fat diet that’s bad lead to higher mortality and if you eat a very high carbohydrate diet that’s also bad. It’s basically what they found there was no there was no low anywhere, other than the very high carbohydrate diet was what you might call a very low fat diet. And that they found to be very detrimental and lead to higher mortality.

Shelley – What would you consider to be a true low carb diet.   If 30 percent or excuse me if 37 percent is not a low carb diet what is what is?

Ron Rosedale:  You’d have to get down to about 15 percent. Up considerably lower than what they were testing at. George Cahill at Harvard showed this — that if you don’t get down that low you’re not going to efficiently burn fat. You’re really not going to burn fat as your primary fuel unless you get down that far. And the reason for that is the reason we stated about the effects on hormones. So you really have to get down there.  A major problem with this study is that, first of all I mean there are a lot of things, there’s so many problems with it. Not the least of which is what we talked about there when there was no low carbohydrate diet group to begin with.

Challenges with Food-Recall — from the 1980s

And the reason for that is, what they studied, it was an epidemiologic study. It was a population study. Epidemiologic studies are difficult to begin with because they have so many variables that you have to account for if you can.   The problem is you can never account for all the variables because you don’t know all variables nor do you typically get data on all the variables. In this particular study it was a questionnaire. And so number one is an epidemiologic study. Number two they used questionnaires and many studies have shown that when you ask people what they’ve eaten, especially when they have to reflect on it, if you ask the question, “What did you eat last week; what did you eat yesterday?” They’re notoriously wrong. And you can speculate as to why they’re wrong.   Many people feel guilty for instance if they ate two milkshakes yesterday and french fries, they’re not going to report that–they might report one milkshake. They didn’t report that they ate too much. There’s kind of a guilt and especially when it pertains to higher fat. You know that the fat has been so vilified that people are just reluctant to admit that. So anyway whatever the reason we know that food questionnaires are fraught with inaccuracies. So that’s another problem with this study. It began in the 1980s and in the 1980s there was there was no such thing as low carb–that it wasn’t even a phrase. So virtually nobody was eating low carb because everybody was told that that you should eat high carbs. And that’s a major major problem then with an epidemiologic study.  Also, we mentioned that there’s a lot of confounding variables, and in this study there were at least at least one major one. Actually are two major ones. One you can’t blame them too much for, because in the days when this data was collected, they just didn’t know anything about TOR (the target of rapamycin), but they did know about Ferritin. 

Facing up to Ferritin (and Foods High in Iron)

Ferritin–too much iron is very bad for a person. If it accumulates we know that iron rusts, for instance and it actually literally rests inside your body too and it can kind of rust the lining of your arteries and burn the lining of your arteries. It stores in tissues such as the pancreas and we know that high ferritin is very associated with diabetes.   Ferritin is a reflection of how much iron a person eats. I knew when I was seeing diabetics every now and then you’d find a diabetic with a very high Ferritin levels and you could literally reverse that person’s diabetes if they did nothing else, just by lowering their ferritin. And so ferritin is also very highly correlated with mortality.

Shelley – What is there diet that tends to lead to higher iron levels, high ferritin levels.

Ron Rosedale – Great question. The major factor, really about the only food that can really shoot up ferritin levels and iron levels, and this can be a an additional factor that causes a greater rate of death i.e. mortality, is red meat. And so people who eat a high red meat diet have to really measure their ferritin, but it’s just rarely done. There’s no money in it for anybody. There’s no drug that really lowers your ferritin, and so it’s not paid attention to.   But it’s a really simple variable that can be accounted for, certainly in a study like this — it’s there but only indirectly — the study conclusions did point out that people who got their protein from plant-based sources tended to live significantly longer than people who got their protein from animal sources.  A lot of animal based protein comes from red meat which contains high ferritin.  And that’s really the point that we’re making–the researchers came to the conclusion that animal-based protein is more hazardous,  because in their statistics they did not account for ferritin.   That’s even though the association with ferritin and mortality is well known.  In other words had they corrected for ferritin levels I think they would have it would have negated the difference in results they had with mortality in a plant based versus animal based diet, because there’s such a high correlation of mortality and ferritin. They came to the conclusion that animal protein was bad as opposed to plant protein, but that was a false conclusion I believe. Ferritin, they didn’t account for that.  Had they accounted for that I think it would have eliminated the vast majority of their (negative) results (regarding animal versus plant protein).  It would not have been the protein source that led to higher mortality–it would have been the iron.   The animal protein consumed was mostly red meat which is lamb, beef even chicken to some extent has red from blood. And that raises ferritin, but they didn’t measure ferritin, and they didn’t compensate for that ferritin when they came to their mortality conclusion.  ((NOTE – For someone who has high ferritin levels, Ron Rosedale recommends giving blood to reduce high iron levels)

The Target of Rapamycin (TOR) and the problem of high protein consumption

The other major confounding variable that was not accounted for and this is probably because they didn’t know anything about it. And that’s again a problem with epidemiologic studies that you can’t account for things you don’t even know about. It had to do with a pathway called the mammalian or sometimes now it’s called mechanistic, and you should even forget about the I think.  It should be called the target of rapamycin.  That’s a newer pathway that is now extensively being studied. It’s a pathway that now has been attributed to the longevity and health benefits of calorie restriction diet, for instance. So it’s an extremely important pathway. It’s a very ancient pathway that regulates almost all life metabolism.  The pathway is influenced by all sorts of different nutritional inputs, such as the amount of energy, the amount of ATP which is kind of an energy battery, insulin, leptin but it’s also influenced by nutrients.  The most powerful stimulant of Tor is protein. The most powerful stimulants within protein are the branch chain amino acids and particularly something called leucine, which is a particular amino acid that is found much higher in animal protein.  Animal protein has long been considered a much higher so-called quality protein — that’s how it’s described in scientific journals. In contrast, plant proteins are deficient in many essential amino acids  ((Vegetarians get complete proteins by eating complimenting foods together)). But the relevance here is that plant proteins don’t elevate the target of rapamycin near as much as animal proteins.

Shelley – Is  it good or bad to have high TOR?

Ron Rosedale — Well it’s probably good early in life. This would get us into probably a longer talk than we have time for as far as the biology of aging. But prior to reproductive years it’s good to have higher TOR because you need it you need to grow.  You need to grow muscles and you need it just to grow up, so that you can become an adult.   But after reproduction — basically after middle age, then an elevated TOR starts causing lots of problems and we know elevated TOR can increase risk of cancer and an increased risk of death from other causes as well, which is why lowering the Target of Rapamycin is more known today.   There is even a drug that lowers it. And we know that that is the first drug that actually has been shown to lower TOR also very convincingly reduces the rate of aging in laboratory animals. That’s pretty cool. So in other words TOR really is a powerful pathway, and it high TOR raises its ugly head after middle age. If you raise TOR after middle age, it increases the risk of cancer, and it increases risk of mortality.

Shelley – What I hear you saying is that if someone is eating a lot of protein after middle age, they increase the likelihood that their TOR levels will be high. And if somebody wants longevity they might want to have moderate but not too much protein–ie, less than most Americans eat, in order to give them a better chance at longevity.

Ron Rosedale – That’s exactly correct. But in this study what is particularly relevant is you can eat more plant protein without raising TOR, compared to eating the same number of ounces of animal protein.  That’s because plant protein is “lower quality”  it’s less usable, and so you can eat more of it because eating more plant protein is like eating less animal protein.

Shelley – The Lancet study does seem to indicate that people who ate plant based proteins were more likely to live longer than people who ate animal based proteins.

“Rather than saying that animal protein leads to higher mortality, they could have just said that eating too many much branch chain amino acids, for instance, will lead to higher mortality, and that’s probably true.” – Ron Rosedale

Ron Rosedale – That’s correct.   But the confounding variable that they did not account for was the quality of the protein, in terms of them measuring the “amount” of usable protein in plant versus animal protein.   To figure that out, they could have just measured the amount of leucine–it’s actually quite easy to measure in a food-based analysis.   And rather than saying that animal protein leads to higher mortality they could have just said that eating too many much branch chain amino acids, for instance, will lead to higher mortality, and that’s probably true. In other words, it’s not the fact that it is an animal or a plant.  It is the fact that you have more usable protein in the animal protein.

Shelley – And people in the United States tend to eat an excess amount of protein compared to what their body actually needs?

Ron Rosedale – Exactly. And that will lead to higher mortality. In the same vein, the other reason that, calorie for calorie, a plant based diet can show greater benefits than an animal based diet is because a plant based diet is much higher in cellulose.  Cellulose is the stringy part of, let’s say celery.  Cellulose is fiber.  It’s not digested. So you hear the adage you are what you eat. But that’s not really true. What is much more true is that you are what you don’t excrete, and when you eat a bunch of plants, basically some “calories” are actually fiber, and they go right through you. You basically poop most of it out and so you don’t really eat it; you don’t absorb it. And so it’s a way to eat less without it being counted as eating less.

I don’t care whether a person eats plant or animal protein. It doesn’t make any difference really–what is important is the amount of absorbable protein, and the amount of absorbable carbohydrate. And the same can be said for fat. And so that’s what needs we can in other words what are you really eating what are you eating that’s actually getting absorbed and doing something. And yet if it just goes in and out of you it’s it shouldn’t really be counted. And so if you eliminate that portion what you’re really seeing is that if two groups eat the same so-called calories in one group is eating a bunch of cellulose from plants they’re actually eating them they’re actually eating much less. And so that wasn’t accounted. 

The Types of Fat

Ron Rosedale – Also the types of fat weren’t accounted for. And that’s easy to measure. We know the benefit for instance of fish oil and how much omega 3 someone eats, whether from plant or animal sources.   How much mono unsaturated versus polyunsaturated fat for instance.   Walter Willett ((author of this study)) he’s done a lot of great papers but this I think was not his greatest hour. 

“Einstein once said that you want to keep things as simple as possible but not too simple.  You don’t want to keep things too simple because it will make it wrong.  And what they did in this study, is they kept things too simple.” – Ron Rosedale 

Shelley – Would you like it if the researchers would make available the entire database of what they collected over 25 years in these informational interviews, to see what else could be teased out of the study from people looking through different lenses?

Ron Rosedale – My guess is they would have they would have then come to no conclusions. I think it would have shown nothing because of the the other factors.  For instance, even if they did have a very low carbohydrate branch in this study, there would probably be too few who ate that way for statistical analysis because, really nobody was eating a very high fat, very low carb, adequate protein diet in the 1980s.  And that’s the other major problem in that you know we haven’t even talked about the major problem in this study. Now Einstein once said that you want to keep things as simple as possible but not too simple and you don’t want to keep things too simple because it will make it wrong.  And what they did in this study, is they kept things too simple. You can’t just measure the amount of carbohydrate and compare it to everything else.  When I first started talking about high fat – low carbohydrate diets in the  late 80s and early 90s, nobody was talking about it then.  But I knew even back then and there were maybe four or five other people in the world that were talking writing about low carbohydrate and they were all high protein. But at the time people didn’t really pay that much attention because they were just thinking about low carbohydrate. But since we now know, and I’m very happy because I’ve been pushing a high fat instead of a high protein diet for the last quarter century, there’s a huge difference between a low carbohydrate high fat diet and a low carbohydrate high protein diet.

“There’s a huge difference between a low carbohydrate, high fat diet and a low carbohydrate, high protein diet.” – Ron Rosedale

 And the vast majority of people who were undertaking a low carbohydrate diet since they started since we started talking about it in the late 80s and beyond, they gravitated to a high protein diet because fat had been so vilified.  It’s only been very recently that the the falsity of the detriment of high fat is coming to light.  They’re not even talking about low carbohydrate diet anymore. They’re talking about ketogenic diets and that’s also a name I’m not really fond of ((because consuming excess protein can increase ketone production as well)), but they talk about it because in general, ketones are chemicals that are produced when you burn fat.  It’s not the it’s not the fact that you’re eating low carb it’s the fact that you’re allowing the burning of fat and that allowing the burning of fat is what we talked about earlier.  By regulating hormones that tell you whether you can burn fat, it regulates insulin and leptin and Tor, so you eat to regulate the hormones that tell you whether you can burn fat or not.

And so you can’t just talk about low carbohydrate and compare it to everything else which is what this study did. And that’s really the major problem with it. So not only did they not have a low carbohydrate diet, but they then lumped low carbohydrate with anything else. They didn’t tease out: Was it a low carbohydrate high fat? Was it a low carbohydrate high protein in their mortality statistics?  They didn’t tease it out. 

Shelley – Are you concerned that this kind of study and the way that it’s been reported, ie publicity asserting that you live longer you eat over half your calories is carbohydrates–this may scare a lot of people into avoiding trying a very low carb diet?

Ron Rosedale – Yes I am very concerned. I think that papers such as this are extremely dangerous because diet is so important to a person’s health. I mean everybody’s heard that you know. Yeah what they eat is important. People don’t understand how important it is.  By influencing diet in laboratory animals you affect the rate that they age.  That’s huge. You affect the most important pathways in the body that regulate cardiovascular disease and cancer such as the TOR pathway.  What you eat is extremely important.  And so people authors such as this have to show greater responsibility.

Shelley – If you were to start this kind of study today to get the kind of information you think would be of use to people, what would you do?

Ron Rosedale –  Well the problem is it’s very difficult to do human mortality studies because you have to wait at least a generation. You know it would be a study that would take 50 years and most people don’t want to wait that long.   Certainly most researchers don’t, because the results of the research wouldn’t come in until after most of them had died. But you can glean at least something from animal studies.  The basic pathways that regulate metabolism have been around almost since animals have evolved and the reason for that is those pathways are so important that they they weren’t mutated away.  Any type of major mutation to these major pathways would have led to death, so that species wouldn’t be around today. So the major pathways, the major metabolic hormones Tor and insulin and leptin, they’ve been around for a very long time.

“You just have to do it and then you’ll see huge benefits,” Ron Rosedale

Shelley – What do you recommend for health — 15% carbs, 15% protein, 70% fat?

Ron Rosedale – (YES — HOWEVER . . . ) if you are going to go on a low carbohydrate diet you really have to go on a low carbohydrate diet. You can’t do it. Well I don’t know if I can say this on air but you can’t do it half assed You’ve got to do it. You’ve got to go on a low very low carbohydrate diet and substitute good fats into the type of fat make a big difference. And so it has to be done properly. You can’t just do it haphazardly and you can’t do it half assed. You just have to do it and then you’ll see huge benefits. Best thing you can do.

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Down Syndrome and Inflammation — Joaquin Espinosa, PhD — Extended Version

Espinosa Lab VisualDown syndrome and Inflammation ((EXTENDED VERSION))  Joaquin Espinosa,  executive director of the Crnic Institute for Down syndrome, discusses the inner workings of cells in people with the genetic mutation known as Down syndrome.  His findings may explain some common characteristics of Down syndrome, such as shorter stature, cognitive challenges, protection from some cancers, and increased risk of pneumonia and Alzheimer’s.   Espinosa’s lab used Boulder’s Somalogic protein analysis tool to inspect thousands of the different proteins our bodies make.  The lab discovered a few hundred proteins that are noticeably different for people with Down syndrome.  These proteins do not specifically influence height or how to take a test.  Instead, they reveal an out-of-balance immune system.     PRODUCER – Shelley Schlender

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TRANSCRIPT:  

Joaquin Espinosa PhD  Transcript of Interview with Shelley Schlender Aug 2018

Joaquin Espinosa: I’m Joaquin Espinosa. I’m a professor of pharmacology at the University of Colorado Anschutz Medical Campus. I’m also the executive director of the Linda Crnic Institute for Down Syndrome at the Anschutz Medical Campus.

Shelley Schlender: In your lab you work on cancer and Down syndrome.

Joaquin Espinosa:  Correct. I have two research teams. One of them is focused on cancer research. One of them on Down syndrome but as we may be able to talk later there are connections between these two conditions.

Shelley Schlender: Do you know some people with Down syndrome.

Joaquin Espinosa: I do.

Shelley Schlender: What are they like?

Joaquin Espinosa: Oh they are fascinating. First of all no two people are the same. With or without the syndrome, so I don’t want to generalize about people with Down Syndrome. But there are some patterns, some qualities that are common among people with Down syndrome. They’re very kind. They’re very accepting very loving. So they’re really a great presence.

Shelley Schlender:  Yes I’ve heard that many times that people with Down syndrome there’s a way that in their presence they remind all of us of some of the most magical and special parts of being alive and being with other people.

Joaquin Espinosa:  Yes they have a joy of life. They are also very emotionally intelligent. I think they can perceive even ahead of yourself your emotional state. They can sense if you’re stressed or if you are happy and they can, interact in that way with you reading you at the emotional level very well.

DOWN SYNDROME —ALZHEIMER’S—AUTOIMMUNE DISEASES—CANCER

Shelley Schlender:  And at the same time people with Down syndrome, by the age of 40, most of them will have Alzheimer’s disease; by the age of 40, most will have some kind of serious autoimmune disorder, and they’re also prone to infectious diseases, and they’re prone to some kinds of cancers but not others.

Joaquin Espinosa:  Yeah — let me elaborate a little bit on that. The Alzheimer’s piece, first of all, yes people with Down syndrome are the largest population with a genetic predisposition to early onset Alzheimer’s disease. And by the age of 40 most of them had the signs of the pathology in the brain, but not necessarily the dementia–the true manifestation of the disease. It may take another 20 years or so for that dementia to develop. And they have a lot of variability, and some of them despite the fact that they had that brain pathology do not become demented until their 70s. So studying people with Down syndrome can really reveal how to modulate the progression of Alzheimer’s disease. It is also true that people with Down syndrome are highly predisposed to autoimmune conditions. Things like Hashimoto’s Hypothyroidism, when the immune system attacks the thyroid gland, celiac disease, rheumatoid arthritis, type 1 diabetes. So a whole range of conditions. The Cancer Connection is fascinating. On one hand, they are protected from most solid malignancies. And what I mean by these is tumours of solid tissues, like breast cancer, prostate cancer, colon cancer, liver cancer–much reduced rates of those.  On the other hand they have higher rates of leukemias, the malignancies of the blood cells. So there is something very interesting going on there.

Shelley Schlender: They get some kinds of cancers they don’t get other kinds. They’re more prone to the placquing of Alzheimer’s disease though some may not show signs of dementia till a later age. They are definitely more prone to autoimmune diseases. Now you did a study that involved an extensive look at proteins and how proteins expressed in the bodies of people with the genetic condition we call Down Syndrome. What is special about a protein study why would you study proteins.

5,000 PROTEINS—IMMUNE SYSTEM “HYPERACTIVATION”

Joaquin Espinosa: So we did two studies and they’re related. One was looking at the proteins in the blood. Let me remind you that our genetic information goes from DNA which is packaged in our chromosomes. It produces a molecule called RNA and then the RNA then becomes translated into proteins so more or less, for every gene in the human genome and there are like 20,000 genes you would find a protein somewhere or another in the body. So if you want to study the genetic information, the genetic makeup of an individual, or any organism, looking at collections of proteins could be very informative.

Shelley Schlender:  In studying proteins do proteins do all the jobs in the body.

Joaquin Espinosa:  Not all of them but many, if not most of them.

Shelley Schlender: So by studying proteins in the body you can get some ideas of what kind of jobs is the body doing what kind of jobs might it be doing too much and what kind of jobs might it be doing too little.

Joaquin Espinosa:  Correct.

Shelley Schlender: So you studied the proteins between people with Down syndrome and also people who don’t have Down syndrome. Where were the variations.

Joaquin Espinosa: We looked at almost 5,000 proteins in the blood of people with and without Down syndrome, and we found about 300 that were very different, meaning they were significantly elevated or significantly depleted in people with Down syndrome, and about half of those proteins had to do the immune system.

Shelley Schlender:  The immune system. Is that what people have normally thought is the area of a person with Down syndrome that is different from other people.

Joaquin Espinosa: It was noted here and there in the literature that people with Down syndrome have differences in the immune system but nobody had done this unbiased analyses of thousands of proteins that would place the immune system at the top of the chart as the top category of what is different in people with Down syndrome.

Shelley Schlender:  When people think about Down syndrome, they usually think about somebody who doesn’t do as well on standardized school tests–yet it’s the immune system that you found is different.

Joaquin Espinosa:  Correct. And everything that we talked about–the different disease spectrum, people with Down syndrome having more Alzheimer’s. less solid tumors, more leukemia but also the cognitive aspects. All of it could potentially be explained by these differences in the immune system. Let me elaborate a little bit on the role of the immune system in the brain, since you brought that up. Yes people with Down syndrome have cognitive differences. About 15 percent of the cells in our brains are immune cells that are called the microglia. These are cells that are sitting in our brains to protect the neurons and other cells in the brain from infections. In Down syndrome, the microglia, the immune cells of the brain, become hyperactive. They produce toxic compounds that will basically poison your brain. So even the cognitive aspect of Down syndrome could be explained by a hyperactivation of the immune system.

Shelley Schlender:  You just said hyperactivation, meaning that it looks like the immune system is working too hard. Working so hard that it’s doing some wrong things in people with Down syndrome.

Joaquin Espinosa:    Correct. The immune system has many branches. It’s not the same branch of the immune system that we use to fight off a virus than it is to fight off a bacterial infection. So what we’re seeing is a particular aspect of the immune system involving the viral defense and the tumor defense, called the interferon response, because it interferes with viral replication. In Down syndrome that is hyperreactive. But when you’re doing too much of something, even if it were to be a good thing, of course you can see exhaustion and you can see it eventually wear out the system. So we like to say that the Immune system of people with Down syndrome is generally out of balance.

Shelley Schlender:  Do you mean that there’s too many of these immune cells doing things, or do you mean the immune cells are exhausted and they’re working too hard trying to do things that they really don’t need to be so worried about.

Joaquin Espinosa:  We see both, which is some type of immune cells that people with Down syndrome have more of and they are more active. For example the cells that are involved in fighting off tumors. Now the cells that are involved in fighting off tumores are the same cells that could cause autoimmunity because rather than attacking a tumor they start attacking a healthy tissue. There you go you have an autoimmune disease.

Shelley Schlender:    Meaning that the cells started out, we hope, fighting something that needed to be fought in the body. But then it got confused and it said Well this other cell looks a little bit like the cell I was fighting. So maybe I should fight it too. And it happens to be a cell that’s part of our body that is fighting now.

Joaquin Espinosa:  Correct. When the vigilantes in your body are hyperactive the chances of making a mistake increase. And that’s what we’re seeing. But there are also other aspects of the immune system that are depleted–the immune system is out of balance. Some parts are too active. Some parts are weakened.

Shelley Schlender:  In the case of somebody with Down syndrome your research indicates that they may have the dial turned up to high on attacking cells that, to the immune system, like similar to viruses . . . including body cells that look somewhat similar to viruses. But on the other hand if somebody with Down syndrome gets a bacterial infection, they’re prone to get really sick from it.

Joaquin Espinosa:  Absolutely correct that antibacterial defenses in people with Down syndrome are diminished. In fact bacterial pneumonia of the lung, you know, lung pneumonia, is the top cause of mortality among people with Down syndrome. Few people know that. So this is a main concern for us, and an area of intensive research. How can we normalize the immune system so that we tone down the aspects that are hyperactive and at the same time we build up the antibacterial defenses that may help these individuals fight off the pneumonia.

DRUGS & OTHER INVESTIGATIONS FOR “TAMING” IMMUNE SYSTEM

Shelley Schlender:  Well how about using some of the standard immunotherapies such as using a steroid drug to just suppress the whole immune system, etc.

Joaquin Espinosa:  Steroid Drugs will not produce the type of rebalancing that we would like to achieve. But there are other approved drugs used for some auto-inflammatory conditions like rheumatoid arthritis for example. These drugs are called JAK inhibitors (Jakinibs, or Janus Kinase Inhibitors) which we think will do a better job than just a corticosteroid. So we are testing these drugs in animals models. We have mouse models of Down syndrome, that is mice that have an extra chromosome, just like people with Down syndrome do. But also we know now of some individuals with Down syndrome that have taken these drugs for some of their autoimmune conditions and they’re seeing benefits. So we are also planning on eventually doing the appropriate clinical trial to test these immune therapies that could bring back the immune system to a state of balance.

Shelley Schlender:  Are you envisioning that a course of treatment with one of these drugs could get the immune system to a place where can take care of itself. Or are you thinking that this would be a lifelong using of a drug or a nutritional approach or something, that would help rebalance the system in an ongoing way.

Joaquin Espinosa:  I don’t think it would be a treatment that you would take for only a few weeks or a few months and then you kind of stop it. This is more like a chronic inflammatory condition. So examples will be rheumatoid arthritis or autoimmune conditions like celiac disease. So you have to be on a chronic treatment. Now when you do a long term treatment of course the concern is for undesired side effects appear if you’re going to tone down the immune system. You want to make sure you don’t do it too much. Otherwise you will increase the risk of some viral infections. To give an idea we have people with rheumatoid arthritis that have been taking these immune therapies for 20 years now and they continue to take these pills everyday. So it is possible to envision that people with Down syndrome would be on some kind of immune therapy from an early age. How early. We don’t know the research will have to be done and then continue with this for lifelong benefits. You did mention something about changes in the nutrition this is something that we’re very interested in. Are there types of anti inflammatory diets that could help people with Down syndrome. We hope so. I mentioned to you that people with Down syndrome are more likely to develop celiac disease So in those with a diagnosis of celiac disease. Of course a gluten free diet will have profound benefit.

Shelley Schlender:    Are there any other nutritional interventions or exercise interventions that you think might be helpful.

Joaquin Espinosa:  In terms of nutrition where we’re paying attention to everything that people with Down syndrome have been taking. There are a number of dietary supplements that families have adopted here and there. And as part of our research we have a cohort study of the population with Down syndrome where people with Down syndrome and their relatives provide us with biological samples but also with medical information and lifestyle information. So we’re recording all these data and if any of these dietary supplements were to have a benefit on the immune system we’ll probably pick it up during the course of this study. We’re not there yet. We have almost 500 participants in this study. To do this type of research we’ll probably need thousands of participants to have enough who are taking a supplement versus enough who or not taking the supplement to be able to do that research.

Shelley Schlender:  How about things like how much carbohydrate does someone eat compared to how much fat compared to how much protein.

Joaquin Espinosa:  We’re looking at the metabolism of people with Down syndrome in fact we published a paper last year and we have another one in preparation where again we looked at the blood and the plasma, and we measured various kinds of fats, carbohydrate, amino acids. And there are some differences in metabolism. Whether those differences then can be interpreted in a modification to the diet that will help the immune system, it’s early days to get there, but there is evidence that people with Down syndrome may metabolize certain nutrients in a different way.

Shelley Schlender:  And how about hormones. Did your test look at insulin levels? Cortisol levels?

DOWN SYNDROME – HIGH LEPTIN — SLEEP APNEA

Joaquin Espinosa:   We have looked at several hormones. Not all of them. We’ve found that a hormone called leptin, which is involved in energy metabolism but also control of appetite, is disregulated in people with Down syndrome who have obstructive sleep apnea. So it turns out that about half of people with Down syndrome have a sleep disturbance where they have, basically a problem with airflow during the night and they wake up many times during the night. There are some treatments that one could do for such as C-Pap. So we have noticed in our study that those that have obstructive sleep apnea have deregulated leptin levels. It has been noted in the literature in typical people that if you have obstructive sleep apnea, your metabolism may change and you may actually put on weight. So that is just one example of how one of the co-morbidities of Down syndrome, in this case a sleep disturbance, can then impact the metabolism and body weight.

Shelley Schlender:  Or Vice versa. It’s not clear whether the disregulation of leptin is leading to more sleep apnea or the other way around. But you also said disregulation–does that mean that people tend to have higher levels of this hormone called leptin, or do they have levels of the leptin that are too low? How is leptin dis-regulated.

Joaquin Espinosa:  Leptin is elevated in the plasma of people with Down syndrome and obstructive sleep apnea. But what happens when you are constantly exposed to high levels of a hormone, you may become desensitized to it and you may acquire what is called leptin resistance. Yes you have more of it in the blood, but actually you respond less to it. You have become desensitized. So that’s why I use the word disregulation.

Shelley Schlender:  That’s similar to insulin resistance where somebody has high levels of insulin but their cells can’t hear the signal. Do people with Down syndrome tend to have high levels of insulin as well?

DOWN SYNDROME TYPE 1 DIABETES

Joaquin Espinosa:  No. What we see in down syndrome is is more of that type 1 diabetes the autoimmune juvenile diabetes, where the new system makes some mistake and attacks the beta cells in the pancreas that produce insulin. So that is why we see more of it– with that being said this is not a highly prevalent condition in Down syndrome.

Shelley Schlender:  And so the leptin is usually high but the insulin is not usually at an unusual level. Well it sounds like you’re finding out a lot of fascinating information that may also inform people about other diseases such as Alzheimer’s such as cancer formation, such as immune system activity for protecting people against pneumonia.

DOWN SYNDROME FEWER ALLERGIES

Joaquin Espinosa:    Correct. So this extra chromosome–chromosome 21 has about 200 genes that people with Down syndrome have an extra copy of — a 3rd copy — clearly it’s regulating human biology in myriad ways, predisposing to some conditions or protecting from others. So it gives us a unique discovery platform to understand human biology and human disease. And we talked about the major examples Alzheimer’s cancer autoimmune conditions but there are many other conditions that are either more elevated or less frequent in people with Down syndrome. For example, people with Down syndrome have more autism, more epilepsy, but they have less allergic sensitization–fewer allergies of a certain type and I could go on and on. So this small more chromosome is really loaded with a treasure of information about human biology or human disease.

 

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Chasing New Horizons – full extended interview

51m+Ih4C2FL._SX327_BO1,204,203,200_Here we provide the full interview by How on Earth’s Joel Parker of planetary scientists Dr. Alan Stern (Southwest Research Institute) and Dr. David Grinspoon (Planetary Science Institute), about their new book: “Chasing New Horizons: Inside the Epic First Mission to Pluto“. Their book describes the the story of Pluto and NASA’s New Horizons mission, bringing the reader backstage to hear the details and meet the personalities behind building, launching, and flying this audacious mission.

Excerpts of this interview were first broadcast on KGNU on May 15th and May 22nd.

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The Moral Arc – Extended Interview with Michael Shermer

The Moral Arc Book CoverShelley Schlender talks with renowned skeptic Michael Shermer about his new book, The Moral Arc:  How Science and Reason lead humanity toward truth, justice and freedom.  This is an extended version of the interview.  (27 minutes)

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MDMA for PTSD – Extended Interview with Karen, PTSD Survivor

Karen - MDMA for PTSD Study Participant

Karen – MDMA for PTSD Study Participant

This is an exended interview with a survivor of treatment resistant post traumatic stress disorder, also known as PTSD.  Karen says she is cured of her PTSD now, thanks to a treatment that includes lots of psychotherapy, plus three times when she took a dose of the psychoactive chemical, MDMA.  MDMA is classed as a federally illegal drug.  However the FDA has approved the drug for use in clinical trials of an intense psychotherapy protocol that includes MDMA.  Now here’s Karen’s story.

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MDMA for PTSD – Extended Interview with Marcella Ot’Alora – Principal Investigator

Boulder Psychiatrist Will Vanderveer

Principal Investigator for Boulder MDMA for PTSD study, Psychotherapist Marcella Ot’Alora

This is an extended interview with Marcella Ot’alora.  Ot’alora is a Boulder psychotherapist, and the principal investigator for the Boulder branch of the FDA approved, nationwide studies of using MDMA in the treatment of post-traumatic stress disorder, also known as PTSD.  MDMA is classed as a federally illegal drug.  However the FDA has approved the drug for use in clinical trials of an intense psychotherapy protocol that includes MDMA.  Now here’s more detail, from Marcella Ot’alora.

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Earth in Human Hands – extended interview

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This is the full interview with Dr. David Grinspoon, author of the book “Earth in Human Hands: Shaping Our Planet’s Future”.  Excerpts of this interview by Joel Parker aired on How on Earth on our January 10, 2017 show.

Listen here:

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