Today, we have a special guest, Dr. Jacoby, who brings a unique surgical perspective to the table. We'll be delving into metabolic health, inflammation, and neuropathy, particularly in the context of diabetes. So, let's dive right into Dr. Jacoby's remarkable journey and insights.

The Surgical Approach: Dr. Jacoby's journey in the field of health and wellness has been truly remarkable, and it all started in Philadelphia. After completing his college education, he found himself at a crossroads, uncertain about his career path. His initial interest led him to podiatric medical school. During this time, he also pursued a degree in chemistry at Villanova, seeking clarity about his future.

A Fortuitous Assignment: Dr. Jacoby's journey took an unexpected turn when he was assigned to work in a laboratory at the Ben Franklin Clinic in Philadelphia. Here, he had the privilege of learning from Dr. Sheff, a renowned expert in the field of biochemistry. Dr. Sheff's work was connected to the discovery of DNA, particularly focusing on Phenyl Keto Urea (PKU), a birth defect affecting the basal ganglia in the brain.

Unraveling Metabolic Health: Dr. Jacoby played a crucial role in this groundbreaking research by conducting experiments on rats. His work revolved around feeding, rendering, and preparing the brains of these animals, which helped Dr. Sheff understand PKU as a metabolic disease influenced by dietary factors.

The Influence of Sugar: One significant aspect that Dr. Jacoby highlighted is the role of sugar, particularly glucose, in metabolic health. He explained how sugar, when combined with proteins, can trigger chemical reactions like the Maillard reaction, causing soft tissues such as collagen to shrink. Moreover, the polyol pathway, activated by sugar, leads to nerve swelling due to increased water retention.

Discovering Dr. Dellon: Dr. Jacoby's path took another turn when he met Dr. Lee Dellon, who was renowned for his work in surgical nerve decompression. Dr. Dellon's breakthrough was in understanding that nerve tunnels in the leg and hand were homologous structures. He found that by decompressing these tunnels, he could restore sensation in patients suffering from neuropathy. Dr. Jacoby was eager to learn and collaborate with Dr. Dellon, which marked the beginning of a new phase in his medical journey.

Unraveling the Role of ADMA: Dr. Jacoby's quest for understanding neuropathy led him to Dr. John Cook at Stanford, who had expertise in vascular biology. Together, they explored the role of asymmetric dimethyl arginine (ADMA) in blocking the nitric oxide pathway. ADMA's ability to disrupt the autonomic nervous system had profound implications for neuropathy.

The Unity of Small and Large Fiber Neuropathy: One intriguing aspect of Dr. Jacoby's research was the realization that small and large fiber neuropathy were not separate entities. Instead, they existed on a continuum. Sugar, specifically glucose, played a pivotal role in causing both types of neuropathy.

Conclusion: Dr. Jacoby's journey through the realms of metabolic health, inflammation, and neuropathy is a testament to the ever-evolving nature of medical science. His work has shed light on the profound impact of sugar and the intricate pathways involved in nerve health. We hope you found this episode as enlightening and thought-provoking as we did. Stay tuned for more exciting topics on our Health and Wellness Podcast, and remember, your health is your wealth.

In this episode, you'll discover:

• Dr. Jacoby's Remarkable Journey: Dr. Jacoby's unique path in the field of health and wellness began with his education in podiatric medicine and chemistry in Philadelphia. He was fortunate to work with Dr. Sheff on groundbreaking research related to Phenyl Keto Urea (PKU) and metabolic health, which involved experiments on rats.
• The Role of Sugar in Neuropathy: Dr. Jacoby emphasized the significant role of sugar, particularly glucose, in metabolic health. He explained how sugar can trigger chemical reactions in the body, leading to the shrinking of soft tissues like collagen. Sugar also plays a key role in nerve swelling, a crucial factor in neuropathy.
• The Unity of Small and Large Fiber Neuropathy: Dr. Jacoby's collaboration with Dr. Dellon and Dr. Cook revealed that small and large fiber neuropathy are not distinct entities but exist on a continuum. Moreover, they highlighted the detrimental effects of sugar on both types of neuropathy. Understanding these insights is essential for addressing metabolic health and neuropathy.

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Transcription

Dr. Latt Mansor:

Yes. Thank you very much. We had some technical difficulties yesterday and thank you for being so flexible and I can't wait to pick your brain around so many topics that are very, very popular amongst our audience around metabolic health, inflammation, neuropathy, you know, diabetes.

It's always being discussed on here and it's always very interesting to get the different perspective from the different experts here.

Dr. Rick Jacoby 

Yes. And I have a very unique approach to this, and that's because I'm basically trained as a surgeon. So most people probably you've had on your show or PhDs or medical doctors who are not surgically trained.So my background goes way back. I don't know how far you want to go back.

Dr. Latt Mansor:

That's great. You know what? We all love a story. Tell us, you know, how far, no matter how far back you go, you know, tell us your whole story, where you started, how you get to where you are today.

Dr. Rick Jacoby

Well, it's, it's a long story. Started back in Philadelphia. I was, when I graduated from college, really didn't know what I wanted to do. But I was interested in going to podiatric medical school, which I did. But the, in the interim, I went to Villanova for chemistry.

Dr. Latt Mansor:

Podiatric is to do with feet?

Dr. Rick Jacoby

Just graduate work in chemistry, really kind of to find out what I wanted to do.

So, I got accepted in Philadelphia, Pennsylvania College of Podiatric Medicine. And I was fortunate in those days I was assigned to a laboratory because we worked when we went to school in those days. I don't know if that's still true. You just take out government loans, but we didn't. And I was assigned to the Ben Franklin Clinic in Philadelphia.

And it was Dr Sheff, he was a PhD MD out of London, he worked with Watson and Crick and he taught biochemistry in Philadelphia. So I was his research assistant. So I always like to say I was one, once removed from Watson and Crick. Yep. And, and,

Dr. Latt Mansor: 

and for those, those who do not know who Watson and Crick are.

Dr. Rick Jacoby:

Yeah, that, you know, the discoverer of DNA. And that was a new subject for me. Dr. Sheff, and he was working on PKU, which is Phenyl Keto Urea Birth Defect of the Basal Ganglia in the Brain. And, believe it or not, we used to do the experiments on a bench. That's, this is all electronic done now, but we, or I did the experiments at his behest.

I fed the rats. I rendered the rats. I prepared their brains. I fed them different chows. And basically he was looking at PKU in those days as a metabolic disease, which it really is. So it's what you eat. And I didn't fully understand that at that time. I was in his biochemistry course and I just want to make sure I got through that.

You know how difficult that stuff is. And I was in his class, so I did very well. So, he got, he gave me the bug, I graduated, I did my residency in surgery in Philadelphia in Podiatric Medicine. Went to directly out to Phoenix area, settled in Scottsdale. I did general podiatric surgery for many years.

I was fortunate, I, I started the Wound Care Center at Scottsdale. Hospital, maybe 35 years ago, so I had a lot of experience with amputations, diabetic neuropathy, metabolic syndrome, because that's what it was called back then, Syndrome X, actually. And then I ran into Dr. Lee Dellon, and he was giving a lecture on surgical decompression of nerves of the lower extremity.

So, we talked about Dr. Dellon, who is he, what does he do, where is he from. Well, he's an amazing human being, he's at Johns Hopkins. He was originally trained as a plastic surgeon, and in his day, plastic surgeons did the hand surgery. That was not a sub specialty in the 70s and 80s. That became a sub specialty.

So if you had a carpal tunnel, which was very rare back then, you would send in a plastic surgeon. Eventually they become, they become a sub specialty in themselves. And he had a patient in the 80s who had, he had done a carpal tunnel release and a ulnar tunnel release at the elbow. And she said to him Dr. Dellon, I'm a diabetic. Why don't you fix my diabetic neuropathy? He said, well, that's a different disease. And he thought about it. He went to the laboratory, did amazing experiments. If your, your audience likes that sort of thing. Rats put ink on their paws, ran them across paper, decompressed one foot, or paw, and the other paw, put bands around the nerves, silicone bands, to create this effect of compression.

 So, he came to the conclusion that the tunnels in the hand, seems obvious today, but it wasn't then, that the homologous structures of the leg are the same as the hand. Now, I mean, this makes sense. So he found those tunnels, decompressed the lady who had the Ulmer Tunnel and Carpel Tunnel, and she had her sensation restored.

Published his first paper in 1984. And here we are, what, I mean, 40 years later, and it's still not a popular procedure. But he taught me, in about year 2000, And I thought it was a novel procedure. He said, read my textbook, by the way, he's written two textbooks, probably 800 peer reviewed articles. Prolific writer, nice guy, brilliant as they all are.

And he can't get anybody to understand what he's saying. So I read his textbook, went down to Johns Hopkins, I trained with him in peripheral nerve surgery of the lower extremity. Came back, I had my first patient. I said, let's call her Janet. Janet, I said. I have a new procedure, it's the first one I'm going to do in a live patient would you like to do it?

Your twin sister actually had just passed away from diabetes. And she was in a wheelchair and she had multiple amputations. She still had her extremity, but multiple amputations, some of which I did. And I said, I don't know what else to do for you, Janet. And she said, let's do it.

So I did it. So this is in spite of amputation. Yes. Yes. She had that of amputation. You are choosing this other procedure that you're going to tell us about.

It's very similar to the carpal tunnel. So she had no feeling. And, she should have had an amputation, but she's willing to try this, so I did, and she actually did get her feeling back, but I lost her to follow up and about three months later, she came back in the clinic.

And she was walking, she had been in a wheelchair, and she had a sling on her arm. And I'm like, what's going on here? You weren't walking, you were in a wheelchair, now you're walking, but you have this sling on your arm. What happened, Janet? She said, well, my, I couldn't walk. My husband took me to, to Hawaii, and we were climbing on the lava rocks.

I slipped, I fell, and I broke my arm. I want to thank you. That's how it all started. Wow. Yes, that's what I said. This is amazing. Why does that work? How does it work? Now, I had, I kind of had an idea how it worked from Dallin's teaching, so I was all in at that point. So, I've done thousands of those procedures.

We don't have any amputations, but the, right now there's a million and a half amputations a year in the world, and about 100, 000 in the United States, 150, 000 in the U. S. But why does it work? Well, it's so simple when you think about it back to sugar. Sugar is a chemical and glucose is in particular, I'll explain the difference between glucose and fructose and all the other sugars, but glucose is the killer.

So sugar, glucose, Is it goes through the Mallory reaction is number one. So in a sugar plus protein for you biochemist out there, you'll love this. So when you mix them, they cause a chemical reaction goes through a shift base where it's reversible. And then when it goes on, it causes these soft tissue, the collagen, the proteins to shrink.

So think of a nerve inside a shrink wrap, so that's shrinking. The second pathway is the polyol pathway, where sugar gets inside the nerve, goes through enzyme system, L dose reductase inhibitors, it overloads the system, and it breaks down to sorbitol, which is hydrophilic, meaning it brings water into the nerve.

So that if a nerve is swelling, and the covering is shrinking, Dr. Dellon says that's compression. And he's absolutely correct. So I worked with him, and then I, one day, I don't know why I said this, I said, Dr. Dellner, I think there's more to your theory. He said, why don't you figure it out? Now he's written like 800 papers, right?

And I said, well, I will kind of go ask someone in my field. I found a guy up at Stanford, John Cook. He's a cardiologist by training. And we'll talk about cardiology, disease, and heart. And he has a PhD in vascular biology. He studies one molecule, asymmetric. Dimethyl arginine, and I'll explain that in a minute.

And he had written an article in circulation in the year 2004. It's called the Uber marker, if you want to look it up. John Cook with an E. And so I read the article and I went, wow, this is interesting. The biology behind the vasculature of, I think it might apply to the nerve. So I text him. He calls me on the phone two hours later.

Love your idea. Come up to Stanford. Let's work on that. I did. So long story short I took my patients, maybe 160 patients, and measured his molecule against my patient population. I found all these other nerves, including MS, that had elevated ADMA, we'll call asymmetric dimethyl arginine, ADMA. And let me explain what that word means, but asymmetric dimethyl arginine.

I mean, it's arginine amino acid, two methyl groups. They're on one side. Asymmetric dimethyl arginine. You know how biochemistry is. Yeah, there we go. Yeah, let's make it simple. Well, what was that molecule doing was blocking the nitric oxide pathway and why that is a really an important concept. This is back in 2005.

Nobel prize in medicine was just given to Murad and his group for discovering nitric oxide. So this is kind of All new, and Dowland's papers, most of them were written before that was known. So we had those two chemical pathways. So I theorized that ADMA was the first molecule to block the autonomic nervous system.

The other two block actually a large fiber versus small fiber. I don't know if your audience, you want me to go deeper into that. But that was a big question back in 2004 and 5. Because most people thought small fiber, which means Let me go back in the history of how this was discovered, which makes it so difficult.

So they were called A delta fibers, C fibers, blah, blah, blah. And of course, they were being discovered at different times. But if we did metric system, it would mean the very smallest to the very largest. You would measure in millimeters, but that's not how it's done. But when it makes sense, the more work a nerve does, like in computer field, the more insulation you need.

So you need more insulation, bigger wire. If it's very, very small, like hot and cold, and it goes through the skin, the nerves, they're called C fibers, they're non-myelinated, because they don't need any covering because there's sensories all over the body for hot and cold, light touch, things like that, and in the autonomic nervous system.

And then when you get more myelin, more work, more electricity going through the nerve, that's sensory, pain. And then when you get the largest nerves, that's motor. Like if you want to move your arm, it takes a lot of energy. Signal. So that's the basic. But that was not known back then when I was looking at this.

So I theorized that ADMA was interrupting the autonomic nervous system. And there weren't any papers. And Dr. Cook said, well, no one's figured this out. Quit your practice. Work with me at Stanford. And my kids are like 10 years old. I'm a clinician. I'm not a scientist. And I said, well, I'll tell you what I'll write a book and that's Sugar Crush.

It's going to take 15 years to figure all this out. You know how science goes, very slow. Although I did like rats, still like rats. I mean, when you're doing research, you do really become bonded to these little guys. And it has been discovered. So I talked to Dr. Cook. He's now a Baylor for stem cell research.

And we'll kind of segue into the stem cell portion of this. And and he said, well, you were right. And I said, I was right at two points. I told you it would take 15 years and it did. And and it is the first blocker of the nitric oxide pathway. So what does nitric oxide do? It relaxes the endothelium.

It comes through the endothelium and relaxes the muscle around the nerve. And the vasovasorum, which means the blood supply to the nerve. So now we have... The mechanism and action for the first phase of diabetic neuropathy, and I think for every other nerve in the body, but that, that work still has to be done.

So I started to have cognition. I said, wait a minute, these people who are coming into me and I'm saying, are you diabetic? And they said, no, I did my blood tests. I had a nerve conduction test or an EMG. No, I am not. Well, they're measuring large fiber neuropathy and these people have pain. So it's really small fiber.

 And that debate back in that day, 2004 or five, they were separate and distinct diseases, small fiber versus large fiber. They're not, they're a continuum, which just makes sense. And the causative agent is sugar, glucose, but these people are not diabetic. Well, they say they're not. Now that's a good question.

Okay.

Dr. Latt Mansor: Yeah. Because, because you may have that sort of neuropathy and you may have some form of metabolic disorder. dysfunction from a glucose point of view, but it may not be clinically significant enough to be classified and diagnosed as diabetic.

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